Our study aimed to further confirm the clinical significance of the tumour budding activity and cell nest size-based (TBNS) grading scheme in cervical squamous cell carcinomas (SCC).

We applied the TBNS system to assess the prognostic value in an institutional cohort of well-annotated cervical SCC consisting of 312 consecutive cases with surgical resection, no neoadjuvant chemotherapy and higher than stage pT1a. We found that high budding activity, single cell and TBNS grade 3 were more frequently associated with a decreased overall survival (OS) time and disease-free survival (DFS) time (P < 0.001) and several other clinicopathological factors, including lymphovascular space invasion, lymph node metastasis, advanced Federation of Gynecology and Obstetrics (FIGO) stage and deep invasion of the cervical wall (> 2/3) (P < 0.05). On multivariate analysis, TBNS grade 3 was an adverse indicator for OS and DFS independently of age, invasion of the cervical wall and FIGO stage (P < 0.05). By comparison, the conventional three-tiered grading system was not associated with OS and DFS in cervical SCC (P > 0.05).

Our study further confirms that the TBNS grading scheme is robust in prognostic assessment in cervical SCC that outperforms the conventional three-tiered grading system. It is applicable to add TBNS grade into routine diagnostic practice.

To determine the value of intravoxel incoherent motion (IVIM) for quantitative tumor budding (TB) evaluation and prognostic stratification in patients with rectal cancer (RC).

This study enrolled 189 RC patients (training set 148, validation set 41) who underwent IVIM and were subsequently treated surgically within 2 weeks between January 2022 and April 2023. Hematoxylin-eosin staining was used for TB scoring. IVIM metrics were calculated on MRI images using biexponential fitting and histogram analysis. Differences in IVIM histogram metrics between the low-intermediate grade budding (Bd 1 + 2) and the high-grade budding (Bd 3) were analyzed. Multivariate logistic regression analysis was used to build the Combined model. The area under the receiver operating characteristic curve (AUC) was used to assess the diagnostic performance of the IVIM histogram metrics and the Combined model. Kaplan-Meier analysis was employed to estimate disease-free and overall survival rates for patients.

Multivariate logistic analysis showed that the D_25th percentile, D_75th percentile, D_90th percentile, and D_95th percentile were independent predictors of Bd 3 (all p < 0.05). The Combined model incorporating these four factors had the best diagnostic performance, with the AUC, sensitivity, and specificity of 0.852, 73.02%, and 82.35% in the training set and 0.856, 75.00%, and 86.21% in the validation set. Furthermore, the score of the Combined model was significantly associated with worse 2-year overall survival (hazard ratio 6.804, 95% confidence interval 2.214 to 20.909, p = 0.001).

The IVIM histogram metrics could distinguish different TB grades and be used as a preoperative risk stratification tool.

Questions Does intravoxel incoherent motion based on histogram analysis predict tumor budding grades and its prognosis in patients with rectal cancer? Findings The histogram metrics of slow diffusion coefficient are an independent prediction factor of high-grade tumor budding and a risk factor of poor 2-year overall survival. Clinical relevance This combined model, based on slow diffusion coefficient, is a reliable tool for preoperative predicting 2-year overall survival in patients with rectal cancer, contributing to risk stratification and individual treatment.

Tumor budding (TB) is an independent predictor of adverse prognosis in colorectal cancer (CRC), defined as clusters of fewer than 5 tumor cells at the invasive margin of cancer. According to the international consensus criteria (ITBCC), TB should be evaluated from the non-mucinous regions. However, some tumors also contain tumor bud-like structures within extracellular mucin pools, and the prognostic impact of these structures remains unclear. To assess this, we defined a modified tumor budding variable (TB-Muc), representing the highest number of tumor buds/bud-like structures observed in a hotspot (0.785 mm2) at the invasive margin, including extracellular mucin regions. We analyzed the prognostic significance of TB (ITBCC criteria) and TB-Muc in two CRC cohorts (N = 1876). TB-ITBCC was associated with advanced stage and lymphovascular invasion (p < 0.001) but also with shorter cancer-specific survival independent of other prognostic factors (Cohort 1: HR for high vs. low 1.99, 95 % CI 1.32-3.01, ptrend = 0.0007; Cohort 2: HR 1.35, 95 % CI 0.98-1.85, ptrend = 0.037). TB-Muc had a comparable independent association with shorter cancer-specific survival (Cohort 1: HR for high vs. low 1.77, 95 % CI 1.18-2.65, ptrend = 0.006; Cohort 2: HR 1.39, 95 % CI 1.02-1.89, ptrend = 0.019). Our results indicate that tumor bud-like structures in mucin do not provide additional prognostic value and should not be included in TB evaluation.

Tumor budding (TB) is recognized as a complementary prognostic factor for colorectal cancer. However, data on its impact on the survival of patients undergoing neoadjuvant chemoradiotherapy (nCRT) remain limited. This study aims to investigate the role of TB in disease-free survival (DFS) and overall survival (OS) among patients with locally advanced rectal cancer receiving nCRT.

In this systematic review and meta-analysis, an exhaustive search of the PubMed, Scopus, Web of Science (WOS), Embase, and Cochrane databases was conducted, ultimately leading to the extraction of eight studies in the qualitative assessment and meta-analysis.

All the included studies were of high quality. The total sample size comprised 1,941 individuals. Although eight studies were included, nine datasets were extracted, as some studies reported multiple outcome measurements. TB positivity was statistically associated with decreased overall survival of 3.24 (95% confidence interval [CI]: 1.71-6.16) and disease-free survival of 2.54 (95% CI: 1.56-4.15) in patients with locally advanced rectal cancer undergoing nCRT.

Based on the findings of this study, TB negativity was statistically and directly associated with better OS and DFS in patients with locally advanced rectal cancer undergoing nCRT.

Microscopic analysis of tumor budding (TB) may be an essential predictive tool for regional lymph node metastases in colorectal cancer, especially among patients in intermediate stages, who exhibit considerable prognostic variability.

The aim of this study was to assess the predictive power of BT regarding the presence of lymph node metastases and its association with other characteristics related to colorectal carcinoma progression.

This is a cross-sectional, retrospective study with a quantitative approach, focusing on the review of medical records and histopathological reports of patients who underwent oncologic surgery for colorectal cancer.

A total of 153 patient records were examined, with a predominance of the 61-70 age group and a male majority (50.98%). Adenocarcinoma not otherwise specified was the most common histological type (60.78%), with the majority exhibiting moderate differentiation (87.58%). From the total sample, 97 cases (63.39%) exhibited TB, with 51.55% classified as a high budding score. Invasion of adipose tissue/subserosa was the most prevalent, occurring in 46.41% of cases. Regional lymph node metastases and angiolymphatic invasion were observed in 66 and 101 patients, respectively. Cross-tabulation analysis showed a statistically significant association between TB and lymph node metastasis (p<0.05).

The relationship between TB and lymph node metastasis highlights the significance of this histological factor in the risk stratification and prognosis of patients with colorectal cancer, complementing TNM staging. Therefore, the assessment of tumor budding is crucial in histopathological reports, potentially influencing additional therapeutic decisions.

Identifying tumor budding (TB) in colorectal cancer (CRC) is vital for better prognostic assessment as it may signify the initial stage of metastasis. Despite its importance, TB detection remains challenging due to subjectivity in manual evaluations. Identifying TBs remains difficult, especially at high magnification levels, leading to inconsistencies in prognosis. To address these issues, we propose an automated system for TB classification using deep learning.

We trained a deep learning model to identify TBs through weakly supervised learning by aggregating positive and negative bags from the tumor invasive front. We assessed various foundation models for feature extraction and compared their performance. Attention heatmaps generated by attention-based multi-instance learning (ABMIL) were analyzed to verify alignment with TBs, providing insights into the interpretability of the features. The dataset includes 29 WSIs for training and 70 whole slide images (WSIs) for the hold-out test set.

In six-fold cross-validation, Phikon-v2 achieved the highest average AUC (0.984 ± 0.003), precision (0.876 ± 0.004), and recall (0.947 ± 0.009). Phikon-v2 again achieved the highest AUC (0.979) and precision (0.980) on the external hold-out test set. Moreover, its recall rate (0.910) was still higher than that of UNI's (0.879). UNI exhibited a balanced performance on the hold-out test set, with an AUC of 0.960 and a precision of 0.968. CtransPath showed strong precision on the external hold-out test set (0.947) but had a slightly lower recall (0.911).

The proposed technique enhances the accuracy of TB assessment, offering potential applications for CRC and other cancer types.

Disease-free survival (DFS) after neoadjuvant chemoradiotherapy (nCRT) is an important factor in affecting the quality of life and determining the subsequent treatment procedures for patients with locally advanced rectal cancer (LARC). This study aimed to develop a novel prognostic model for predicting the DFS in patients with LARC following nCRT and to verify its effectiveness.

Patients with LARC who underwent magnetic resonance imaging (MRI) and nCRT at our institution between November 2017 and March 2022 were enrolled in this retrospective study. Clinicopathologic data and MRI indicators of all patients were collected and evaluated. All patients were divided into DFS and non-DFS groups according to the presence or absence of local recurrence or distant metastasis. The differences in the b-value threshold (bthreshold) and apparent diffusion coefficient (ADC) values between the DFS and non-DFS groups were compared. The Cox analyses were used to determine the risk factors in predicting the DFS. A merged model was established based on the risk factors, and a nomogram was constructed. The predictive performances of the merged model were validated using the receiver-operating characteristic (ROC) and decision curve analysis (DCA).

Of the 524 patients enrolled, 132 who underwent surgical resection post-nCRT were included in the final analysis. The post-neoadjuvant therapy pathological N stage, extramural venous invasion (EMVI), and bthreshold were independent factors in predicting the DFS. The C-index of the model was 0.688. The area under the curve (AUC) of the nomogram in predicting the 1-, 3-, and 5-year survival rates of patients was 0.731, 0.723, and 0.779, respectively. The DCA demonstrated that the merged model had a greater advantage than either the "all" or the "none" scheme when the threshold probability was between 0.1 and 0.65.

A merged model based on the bthreshold value and clinicopathological features showed the potential to predict the prognosis of patients with LARC after nCRT and surgery.

Tumor budding is a significant prognostic factor in colorectal cancer (CRC) management and is graded as follows: 0-4 buds as low, 5-9 buds as intermediate, and > 10 buds as high. However, the specific prognostic difference between cases with 0 buds (BD0) and those with 1-4 buds (BD1) is not well established owing to a lack of comparative studies. This study aimed to examine and compare the rate of lymph node (LN) metastasis and prognosis by distinguishing between BD0 and BD1 within the low-grade category (0-4 buds) of tumor budding in submucosa (T1) and muscularis propria (T2) CRC. We retrospectively identified 223 cases of T1 and T2 CRC underwent surgery from 2015 to 2018 across three medical institutions using medical records. Pathology, including assessing tumor budding, was subsequently reconfirmed, and the recurrence and survival of patients were evaluated up to December 2023. Patients in the BD1 group exhibited a higher T stage than those in the BD0 group, accompanied by significantly increased rates of lymphovascular and perineural invasion. The prevalence of LN metastasis was 14.8%. No significant differences in LN metastasis were observed between the BD0 and BD1 groups. In a multivariate analysis exploring factors associated with LN metastasis, relevant factors included lymphatic invasion, perineural invasion, and ≥ 5 buds. There were no significant differences in 5-year survival and progression free survival rates between the BD0 and BD1 groups (P = 0.971). This study confirmed that there was no significant difference in LN metastasis or prognosis between patients with BD0 and BD1.

A shorter duration of oxaliplatin adjuvant chemotherapy has recently emerged as a potential option for patients with high-risk stage II and low-risk stage III (T1-3N1) colon cancer (CC). The present study aimed to elucidate the risk factors for recurrence in these patient populations and to identify the appropriate indications for shortened treatment durations. The present study retrospectively analyzed 396 patients who underwent curative surgery for pathological T4N0 or stage III CC, followed by adjuvant chemotherapy, at two institutes. Overall, 234 patients with T4N0 and low-risk stage III CC were categorized into the low-risk group and 162 patients with high-risk stage III CC into the high-risk group. The 3-year relapse-free survival rate was significantly higher in the low-risk group than in the high-risk group. Multivariate Cox model analysis of the low-risk group revealed that high preoperative serum levels of carcinoembryonic antigen (CEA) and incomplete 6-month adjuvant chemotherapy with oxaliplatin were independent poor prognostic factors. The prognosis of patients in the low-risk group who had abnormal CEA levels and did not complete the 6-month adjuvant treatment with oxaliplatin was similar to that of patients in the high-risk group. However, the prognosis of patients in the low-risk group with high CEA levels improved with a 6-month adjuvant treatment with oxaliplatin to a similar level to that of all patients with low CEA levels in the low-risk group. In conclusion, the present study suggested that the duration of adjuvant chemotherapy with oxaliplatin should not be shortened in patients with high preoperative CEA levels, even in the low-risk group.

Oral cancer is one of the most common cancers seen in the Indian subcontinent. Its primary treatment is surgery with or without adjuvant treatment. Despite advances in science, prognosis and overall survival has not yet chanced over the past two decades. Pathologically proven regional lymph node metastasis adversely affects the prognosis. This study was conducted to evaluate the predictive factors for lymph node metastasis in Stage I and II oral squamous cell carcinoma (OSCC) with distinct emphasis on tumor budding and worst pattern of invasion. This is a prospective observational study was done at a tertiary care center, Prince Aly Khan Hospital, Mumbai, over a period of 22 months (March, 2020 to December, 2021). We analyzed 237 patients of early OSCC for clinicopathological parameters (age, trismus, differentiation, depth of invasion, tumor budding, worst pattern of invasion). Chi Square test and logistic regression model were used for data evaluation. Statistical Package for Social Sciences, version 21.0 IBM Corporation USA for Microsoft Windows, was used for data analysis. This study reported statistically significant predictive factors for lymph node metastasis viz. tumor budding (OR 30.8 95% CI 12.365-76.731 p < 0.001), worst pattern of invasion (OR 4.5 95% CI 1.853-11.305 p = 0.001) and age (OR 0.149 95% CI 0.043-0.0516 p < 0.003) on logistic regression model. On Chi square test, along with the above factors- tumor differentiation (p = 0.008) and depth of invasion (p = 0.001) were also found statistically significant in prediction for lymph node metastasis in early OSCC. Strong predictive association exists between lymph node metastasis and tumor budding, worst pattern of invasion and higher age group in early OSCC. These factors can be adapted as a routinely assessed predictive marker and mentioned in histopathology reports with its prognostic implications, thus can be considered for further planning and management. These predictive factors can be used to formulate a risk score to incorporate various clinicopathological factors including tumor budding, worst pattern of invasion, depth of invasion, tumor differentiation and T stage which can be used in patients diagnosed with early stage I & II OSCC where neck dissection can be avoided.

Objective This study aims to investigate the risk factors for lymph node metastasis (LNM) and postoperative recurrence in patients undergoing surgery for pT1 colorectal cancer (pT1-CRC). Materials and methods We retrospectively analyzed 150 patients who underwent bowel resection with lymph node dissection for pT1-CRC at our department between September 2011 and December 2021. Univariate and multivariate analyses were performed to examine the effects of sex, depth of tumor invasion, venous invasion, lymphatic invasion, tumor budding (BD), and histological type on LNM and recurrence. We analyzed recurrence-free survival (RFS) curves. Results LNM was observed in 21 (14.0%) patients. Univariate analysis identified female sex, undifferentiated histological type, positive lymphatic invasion, and tumor budding grade 2/3 (BD2/3) as significant risk factors for LNM, whereas multivariate analysis identified female sex, undifferentiated histological type, and BD2/3 as independent risk factors. No cancer-related deaths were observed during the median observation period of 60.7 months. The five-year RFS rate differed significantly between LNM- and LNM+ patients, at 97.3% and 66.4%, respectively (p=0.0005). BD2/3 was also the significant risk factor for recurrence in the univariate analysis (p<0.0001). In LNM- patients, the five-year RFS was 98.7% for BD1 and 88.2% for BD2/3 (p=0.0014), while in LNM+ patients, it was 100% for BD1 and 37.0% for BD2/3 (p=0.036), with significant differences observed. Conclusion In pT1-CRC patients, female sex, undifferentiated histological type, and BD2/3 were the risk factors for LNM. The recurrence rate was higher in patients with LNM than in those without LNM. Regardless of LNM, BD2/3 was the risk factor for the postoperative recurrence of pT1-CRC.

After endoscopic resection of colorectal cancer with submucosal invasion (pT1 CRC), additional surgical treatment is recommended if deep submucosal invasion (DSI) is present. This study aimed to further elucidate the risk factors for lymph node metastasis (LNM) in patients with pT1 CRC, especially the effect of DSI on LNM.

Patients with pT1 CRC who underwent lymph node dissection were selected. The Chi-square test and multivariate logistic regression were used to analyze the relationship between clinicopathological characteristics and LNM. The submucosal invasion depth (SID) was measured via 4 methods and analyzed with 3 cut-off values.

Twenty-eight of the 239 patients presented with LNM (11.7%), and the independent risk factors for LNM included high histological grade (P=0.003), lymphovascular invasion (LVI) (P=0.004), intermediate to high budding (Bd 2/3) (P=0.008), and cancer gland rupture (CGR) (P=0.008). Moreover, the SID, width of submucosal invasion (WSI), and area of submucosal invasion (ASI) were not significantly different. When one, two, three or more risk factors were identified, the LNM rates were 1.1% (1/95), 12.5% (7/56), and 48.8% (20/41), respectively.

Indicators such as the SID, WSI, and ASI are not risk factors for LNM and are subjective in their measurement, which renders them relatively inconvenient to apply in clinical practice. In contrast, histological grade, LVI, tumor budding and CGR are relatively straightforward to identify and have been demonstrated to be statistically significant. It would be prudent to focus on these histological factors rather than subjective measurements.

Grading lung squamous cell carcinoma (LUSC) is controversial and not universally accepted. The histomorphologic feature of tumor budding (TB) is an established independent prognostic factor in colorectal cancer, and its importance is growing in other solid cancers, making it a candidate for inclusion in tumor grading schemes. We aimed to compare TB between preoperative biopsies and resection specimens in pulmonary squamous cell carcinoma and assess interobserver variability. A retrospective cohort of 249 consecutive patients primarily resected with LUSC in Bern (2000-2013, n = 136) and Lausanne (2005-2020, n = 113) with available preoperative biopsies was analyzed for TB and additional histomorphologic parameters, such as spread through airspaces and desmoplasia, by 2 expert pathologists (M.M., C.N.). Results were correlated with clinicopathologic parameters and survival. In resection specimens, peritumoral budding (PTB) score was low (0-4 buds/0.785 mm2) in 47.6%, intermediate (5-9 buds/0.785 mm2) in 27.4%, and high (≥10 buds/0.785 mm2) in 25% of cases (median bud count, 5; IQR, 0-26). Both the absolute number of buds and TB score were similar when comparing tumor edge and intratumoral zone (P = .192) but significantly different from the score obtained in the biopsy (P < .001). Interobserver variability was moderate, regardless of score location (Cohen kappa, 0.59). The discrepant cases were reassessed, and consensus was reached in all cases with identification of causes of discordance. TB score was significantly associated with stage (P = .002), presence of lymph node (P = .033), and distant metastases (P = .020), without significant correlation with overall survival, tumor size, or pleural invasion. Desmoplasia was significantly associated with higher PTB (P < .001). Spread through airspaces was present in 34% and associated with lower PTB (P < .001). To conclude, despite confirming TB as a reproducible factor in LUSC, we disclose areas of scoring ambiguity. Preoperative biopsy evaluation was insufficient in establishing the final TB score of the resected tumor.

Tumor budding (TB), defined as the presence of individual neoplastic cells or isolated groups of up to 4 cells at the front of tumor invasion, has become an adverse prognostic marker in colorectal cancer (CRC) in recent decades. The prognostic impact of TB in CRC remains not clearly defined and histological methods for its evaluation vary depending on the center. The objective of this study is to investigate the association between TB and CRC, in terms of oncological evolution and pathological stage.

A retrospective observational study was conducted, including patients undergoing curative oncological surgery for CRC between January 2017 and December 2022. The effects of TB on disease-free survival (DFS) and overall survival (OS) were evaluated according to the Kaplan-Meier curves.

In 78 cases TB was described in the pathology report. TB was present in 56 patients (71.8%), divided into the following categories: low grade in 22 (39.3%), intermediate grade in 17 (30.4%) and high grade in 17 (30.4%). The proportion of patients who presented lymph node metastases, lympho-vascular and perineural invasion was significantly higher in patients with TB (26.8% vs 0%, P=.008; 41.1% vs 4.5%, P=.002; 16.1% vs 0% P=.054; respectively). DFS was 86.3% in low-grade TB, 75.3% in intermediate-grade TB, and 70.3% in high-grade TB. Cases with intermediate and high grade were associated with a shorter OS compared to the low grade group (93.7% and 75.4% vs 100% P=.012, respectively).

These results suggest that TB expression may be a useful risk factor as a prognostic factor for the detection of lymph node metastasis, local recurrence, and distant metastasis in CRC.

Tumour budding (TB) is a marker of tumour aggressiveness which, when measured in rectal cancer resection specimens, predicts worse outcomes and response to neoadjuvant therapy. We investigated the utility of TB assessment in the setting of neoadjuvant treatment.

A single-centre, retrospective cohort study was conducted. TB was assessed using the hot-spot International Tumour Budding Consortium (ITBCC) method and classified by the revised ITBCC criteria. Haematoxylin and eosin (H&E) and AE1/AE3 cytokeratin (CK) stains for ITB (intratumoural budding) in biopsies with PTB (peritumoural budding) and ITB (intratumoural budding) in resection specimens were compared. Logistic regression assessed budding as predictors of lymph node metastasis (LNM). Cox regression and Kaplan-Meier analyses investigated their utility as a predictor of disease-free (DFS) and overall (OS) survival. A total of 146 patients were included; 91 were male (62.3%). Thirty-seven cases (25.3%) had ITB on H&E and 79 (54.1%) had ITB on CK assessment of biopsy tissue. In univariable analysis, H&E ITB [odds (OR) = 2.709, 95% confidence interval (CI) = 1.261-5.822, P = 0.011] and CK ITB (OR = 2.165, 95% CI = 1.076-4.357, P = 0.030) predicted LNM. Biopsy-assessed H&E ITB (OR = 2.749, 95% CI = 1.258-6.528, P = 0.022) was an independent predictor of LNM. In Kaplan-Meier analysis, ITB identified on biopsy was associated with worse OS (H&E, P = 0.003, CK: P = 0.009) and DFS (H&E, P = 0.012; CK, P = 0.045). In resection specimens, CK PTB was associated with worse OS (P = 0.047), and both CK PTB and ITB with worse DFS (PTB, P = 0.014; ITB: P = 0.019). In multivariable analysis H&E ITB predicted OS (HR = 2.930, 95% CI = 1.261-6.809) and DFS (HR = 2.072, 95% CI = 1.031-4.164). CK PTB grading on resection also independently predicted OS (HR = 3.417, 95% CI = 1.45-8.053, P = 0.005).

Assessment of TB using H&E and CK may be feasible in rectal cancer biopsy and post-neoadjuvant therapy-treated resection specimens and is associated with LNM and worse survival outcomes. Future management strategies for rectal cancer might be tailored to incorporate these findings.

Introduction: Tumor budding (TB) is considered to be a morphological and prognostic factor relevant to colon cancer (CC). The aim of our study is to assess the TB and to evaluate its relationship to clinicopathological findings within stage II and III CC patients as a single center experience. Materials and methods: A total of 120 CC patients operated between 2018 and 2021 at the University Clinic of Digestive Surgery in Skopje, the Republic of North Macedonia were included in this retrospective, single center study. TB was evaluated by the magnification of 200x along the invasive front of the primary tumor on H&E and CKAE1/AE3 immunohistochemically stained sections. Two grades were used: low grade (TB1, 0-4 TBs) and high-grade, which includes intermediate (TB2, 5-9 TBs) and high grade (TB3 ≥10TBs) of TBs. Results: A statistically significant correlation has been identified between high-grade TB and age (p=0.05) of the patients. There was also a significantly higher occurrence of high-grade TB in patients within stage III CC. Statistically significant correlations were also found in lymph node status (p<0.01), vascular invasion (p<0.05), lymphatic invasion (p<0.01), postoperative relapse (p<0.01), and death (p<0.01). Tumor relapse and death were significantly more frequent in patients with high-grade TB than those with low-grade TB. Patients with registered high-grade TB demonstrated significantly lower relapse-free survival (RFS) and overall survival (OS) rates than patients with low-grade TB over the observation period (RFS: 53.8% vs. 98.5%, p<0.001; OS: 65.4% vs. 97.1%, p<0.001, respectively). Patients with lung and liver postoperative relapses had higher percentage of cases with high-grade TB (94.1%). Conclusion: Our results are highly suggestive that TB should be included as a histological biomarker in the pathology report of patients with stage II and stage III CC, because of its prognostic value.

Colorectal cancer (CRC) is a major public health problem and one of leading cancer related death all over the world. One of the prognostic parameters that play a role in different types of cancer is HER2. However, the role of HER2 in CRC and its relation with clinicopathological features and survival is conflicting. We hypothesize that HER2 has different patterns of expression in CRC which may affect the prognosis of patients.

We studied sixty specimens of colorectal carcinoma for HER2 immunohistochemistry and gene amplification and correlate it with clinicopathological features and patients` survival.

Our data showed that negative HER2 expression was statistically associated with female gender (P = 0.010) and low & intermediate tumor budding (P = 0.030). There was a statistically significant relation between HER2 IHC and HER2 FISH amplification (P=0.000). Although neither HER2 immunoexpression and FISH amplification showed significant relation with overall survival nor disease free survival, HER2 amplified CRCs tended to have a worse survival compared with negative CRCs (40 months versus 50 months). The presence of male gender, lymphovascular invasion, nodal metastasis and distant metastasis (P = 0.013, 0.006, 0.006 and 0.000 respectively) were significantly statistically associated with poor overall survival. The presence of tumor grade III and high tumor budding (P = 0.035 and 0.007 respectively) were significantly statistically associated with shorter disease free survival.

Our results showed that HER2 IHC 3+ staining is highly predictive of HER2 gene amplification in colorectal carcinomas. There is a tendency towards poorer prognosis in amplified HER2 CRC cases.

To assess the value of a multiparametric magnetic resonance imaging (MRI)-based model integrating radiomics features with clinical and MRI semantic features for preoperative evaluation of tumor budding (TB) in rectal cancer.

A total of 120 patients with pathologically confirmed rectal cancer were retrospectively analyzed. The patients were randomized into training and validation cohorts in a 6:4 ratio. Radiomics features were extracted and selected from preoperative T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), and contrast-enhanced T1-weighted imaging (T1CE) sequences, after which the corresponding radiomics score (RS) was calculated, and the radiomics models (T2WI model, DWI model, and T1CE model) were constructed. Logistic regression analysis was selected to develop a combined model integrated RST2WI, RSDWI, RST1CE, and clinical and MRI semantic features. The efficacy of each model in diagnosing TB grade was observed by the receiver operating characteristic (ROC) curve. Decision curve analysis (DCA) was used to assess the clinical benefits of the models.

Seven features were extracted and selected from each T2WI, DWI, and T1CE sequence to calculate the corresponding RS and construct the corresponding radiomics model. MRI reported N stage was an independent risk factor for TB. The area under the ROC curve of the combined model was 0.961 and 0.891 in the training and validation cohorts, respectively. The combined model showed better performance than the other models. DCA showed that the net benefit of the combined model was better than that of the other models in the vast majority of threshold probabilities.

A combined model integrating radiomics features and MRI semantic features allows for noninvasive preoperative evaluation of TB grading in patients with rectal cancer.

There is a need to improve current risk stratification of stage II colorectal cancer to better inform risk of recurrence and guide adjuvant chemotherapy. We sought to examine whether integration of QuantCRC, a digital pathology biomarker utilizing hematoxylin and eosin-stained slides, provides improved risk stratification over current American Society of Clinical Oncology (ASCO) guidelines.

ASCO and QuantCRC-integrated schemes were applied to a cohort of 398 mismatch-repair proficient (MMRP) stage II colorectal cancers from three large academic medical centers. The ASCO stage II scheme was taken from recent guidelines. The QuantCRC-integrated scheme utilized pT3 versus pT4 and a QuantCRC-derived risk classification. Evaluation of recurrence-free survival (RFS) according to these risk schemes was compared using the log-rank test and HR.

Integration of QuantCRC provides improved risk stratification compared with the ASCO scheme for stage II MMRP colorectal cancers. The QuantCRC-integrated scheme placed more stage II tumors in the low-risk group compared with the ASCO scheme (62.5% vs. 42.2%) without compromising excellent 3-year RFS. The QuantCRC-integrated scheme provided larger HR for both intermediate-risk (2.27; 95% CI, 1.32-3.91; P = 0.003) and high-risk (3.27; 95% CI, 1.42-7.55; P = 0.006) groups compared with ASCO intermediate-risk (1.58; 95% CI, 0.87-2.87; P = 0.1) and high-risk (2.24; 95% CI, 1.09-4.62; P = 0.03) groups. The QuantCRC-integrated risk groups remained prognostic in the subgroup of patients that did not receive any adjuvant chemotherapy.

Incorporation of QuantCRC into risk stratification provides a powerful predictor of RFS that has potential to guide subsequent treatment and surveillance for stage II MMRP colorectal cancers.

Tumor budding (TB) refers to the presence of small clusters of tumor cells at the invasive front of a malignant tumor. Single tumor cell invasion (SCI) is an extreme variant of TB, in which individual loose tumor cells are present at the invasive front. Both TB and SCI are important histomorphologic risk factors postulated to indicate loss of cellular cohesion. In this study, we investigated the influence of TB and SCI on different survival outcomes in patients with locally advanced oral squamous cell carcinoma (OSCC).

We included 129 patients with locally advanced OSCC (pT3-4) from a single-center, prospectively maintained cohort. We examined the association of TB and SCI with the presence of occult lymph node metastasis using a logistic regression model. Survival probabilities were estimated using the Kaplan-Meier method and cumulative incidence functions. The association of TB and SCI on overall survival (OS), oral cancer-specific survival (OCSS), and local recurrence-free survival (LRFS) was investigated using Cox's proportional hazards regression models.

TB was detected in 98 (76%) of the tumors, while SCI was observed in 66 (51%) patients. There was a significant association between TB and the occurrence of occult lymph node metastasis (OR=3.33, CI: 1.21-10.0). On multivariate analysis, TB had no detectable impact on survival outcomes. However, SCI showed a higher risk for local recurrence (Hazards ratio (HR): 3.33, CI: 1.19 - 9.27).

This study demonstrates that TB and SCI in locally advanced OSCC function as an independent risk factor for occult lymph node metastases, as well as local recurrences. Both histomorphologic risk factors could serve as an additional parameter for stratifying therapy and escalating multimodal treatment approaches.

Background/Objectives: Recently, some new morphological features of colorectal cancer have been discovered as important prognostic factors; in this paper, we study the relationship between tumor budding (TB) and tumor deposits (TDs). Methods: The retrospective cohort study included 90 patients with pathohistologically confirmed stage III CRC who were treated with radical surgical resection. All hematoxylin and eosin (H and E)-stained slides from each patient were reviewed, and histological parameters were recorded. The samples were divided into two groups with similar sizes: a group without TDs (N = 51) and a control group with TDs (N = 39). The presence and TB grade were further analyzed in these groups and compared with other clinical and histological features. Results: The prevalence of TB in the investigated cohort was unexpectedly high (94.4%). Overall, there were 23 (25.6%) Bd1, 20 (22.2%) Bd2, and 47 (52.2%) Bd3 cases. The presence of TDs was significantly associated with a higher number of TB (p < 0.001, OR 16.3) and, consequently, with a higher TB grade (p = 0.004, OR 11.04). A higher TB grade (p = 0.001, HR 2.28; 95% CI 1.93-4.76) and a growing number of TDs (p = 0.014, HR 1.52; 95% CI 1.09-2.1) were statistically significantly associated with shorter survival. Conclusions: TDs appear more often in patients with higher TB grades in stage III CRC. A higher TB grade and a growing number of TDs were statistically significantly associated with shorter overall survival. These results could give additional emphasis to the importance of TB as an adverse prognostic factor since a strong relationship with TDs has been demonstrated.

This study aimed to investigate the role of SERPINB5 in colorectal cancer (CRC). We established knockdown and overexpression models of SERPINB5 in CRC cells and conducted bioinformatics analysis to assess the clinicopathological significance of SERPINB5 expression in CRC patients. Human CRC cells were transfected with LV-SERPINB5 and sh-SERPINB5 lentivirus for subsequent functional and mechanistic studies. Results showed that high SERPINB5 expression correlated positively with CEA levels, N stage and lymphatic infiltration, while displaying a negative correlation with progression-free survival. Overexpression of SERPINB5 in CRC cells upregulated the expression of TNF-α, p-NF-κB/p65, N-cadherin, MMP2 and MMP9, accompanied by decreased E-cadherin expression. In addition, SERPINB5 overexpression enhanced the migration, invasion, and proliferation of CRC cells. Furthermore, overexpression of SERPINB5 in CRC cells increased VEGFA expression, and the conditioned medium from SERPINB5-overexpressing CRC cells promoted tube formation of HUVECs. Conversely, overexpression of SERPINB5 in HUVECs decreased VEGFA expression and inhibited tube formation. Notably, these changes in CRC cells were reversed by QNZ, a specific inhibitor of the TNF-α/NF-κB pathway. In summary, our findings revealed that high SERPINB5 expression correlated with poor progression-free survival in CRC patients. Moreover, SERPINB5 could induce EMT and angiogenesis by activating the TNF-α/NF-κB pathway, thereby promoting the invasion and migration of CRC cells.

The International Collaboration on Cancer Reporting proposes histological tumour type, lymphovascular invasion, tumour grade, perineural invasion, extent, and dimensions of invasion as risk factors for lymph node metastases and tumour progression in completely endoscopically resected pT1 colorectal cancer (CRC).

The aim of the study was to propose a predictive and reliable score to optimise the clinical management of endoscopically resected pT1 CRC patients.

This multi-centric, retrospective International Budding Consortium (IBC) study included an international pT1 CRC cohort of 565 patients. All cases were reviewed by eight expert gastrointestinal pathologists. All risk factors were reported according to international guidelines. Tumour budding and immune response (CD8+ T-cells) were assessed with automated models using artificial intelligence. We used the information on risk factors and least absolute shrinkage and selection operator logistic regression to develop a prediction model and generate a score to predict the occurrence of lymph node metastasis or cancer recurrence.

The IBC prediction score included the following parameters: lymphovascular invasion, tumour buds, infiltration depth and tumour grade. The score has an acceptable discrimination power (area under the curve of 0.68 [95% confidence intervals (CI) 0.61-0.75]; 0.64 [95% CI 0.57-0.71] after internal validation). At a cut-off of 6.8 points to discriminate high-and low-risk patients, the score had a sensitivity and specificity of 0.9 [95% CI 0.8-0.95] and 0.26 [95% 0.22, 0.3], respectively.

The IBC score is based on well-established risk factors and is a promising tool with clinical utility to support the management of pT1 CRC patients.

Non-curative endoscopic resection of T1 colorectal cancer (CRC) carries a substantial risk of recurrence. However, previous studies have reported a significant proportion of cases in which the deep margin of endoscopic resection was positive for cancer due to the technical difficulties of colorectal endoscopic submucosal dissection (ESD). With the advancement of endoscopic technology and techniques resulting in the reduction of positive resection margins, it is important to reassess the long-term prognosis and major risk factors for recurrence in cases of negative deep margins.

We conducted a retrospective cohort study of consecutive patients with T1 CRC who underwent endoscopic resection between January 2006 and December 2021 with negative deep margins. The histological findings of the resected specimens were analyzed to determine the risk factors associated with the primary outcomes of this study, including recurrence and cancer-related deaths.

The median age of the 190 patients was 70 years, of which 63% were male, and endoscopic treatment was performed in 64% by endoscopic mucosal resection and 36% by ESD. Eighty-two patients were in the curative resection (CR) group and 108 were in the non-curative resection (NCR) group, wherein the latter comprised 79 patients who underwent additional surgery (AS) and 29 patients who did not receive AS. Five-year recurrence-free survival rates were 98.4% (95% CI: 89.3-99.8) for CR, 98.3% (95% CI: 88.8-99.8) for NCR with AS, and 73.7% (95% CI: 46.5-88.5) for NCR without AS. Lymphatic invasion and budding grade 2/3 were the major risk factors for recurrence, with hazard ratios of 40.7 (p < 0.001) and 23.1 (p = 0.007), respectively. Of the patients in the NCR group without AS, the 5-year recurrence-free rate was 85.6% (95% CI: 52.5-96.3) if there were no major risk factors (i.e., no lymphatic invasion or budding grade 2/3) (n = 21), whereas the prognosis was poor in the presence of one or more of the major risk factors, with a median recurrence-free survival and disease-specific survival of 2.5 and 3.1 years, respectively (n = 8).

In endoscopically resected T1 CRC with negative deep margins, lymphatic invasion or budding grade 2/3 may indicate a higher risk of recurrence when followed up without AS.

The aim of this systematic review is to shed light on the role of tumor budding (TB) in the biology, behavior, and prognosis of head and neck squamous cell carcinoma (HNSCC). A search was run in PubMed, Scopus, and Embase databases following PRISMA guidelines. After full-text screening and application of inclusion/exclusion criteria, 36 articles were included. Several investigations support the prognostic role of TB, which might play a role in selecting rational treatment strategies. To achieve this goal, further research is needed for greater standardization in TB quantification. Although TB is not included as a negative prognostic factor in the current management guidelines, it might be reasonable to consider a closer follow-up for HNSCC cases with high histopathological evidence of TB.

Tumor budding (TB) is a powerful prognostic factor in colorectal cancer (CRC). An internationally standardized method for its assessment (International Tumor Budding Consensus Conference [ITBCC] method) has been adopted by most CRC pathology protocols. This method requires that TB counts are reported by field area (0.785 mm 2 ) rather than objective lens and a normalization factor is applied for this purpose. However, the validity of this approach is yet to be tested. We sought to validate the ITBCC method with a particular emphasis on normalization as a tool for standardization. In a cohort of 365 stage I-III CRC, both normalized and non-normalized TB were significantly associated with disease-specific survival and recurrence-free survival ( P <0.0001). Examining both 0.95 and 0.785 mm 2 field areas in a subset of patients (n=200), we found that normalization markedly overcorrects TB counts: Counts obtained in a 0.95 mm 2 hotspot field were reduced by an average of 17.5% following normalization compared with only 3.8% when counts were performed in an actual 0.785 mm 2 field. This resulted in 45 (11.3%) cases being downgraded using ITBCC grading criteria following normalization, compared with only 5 cases (1.3%, P =0.0007) downgraded when a true 0.785 mm 2 field was examined. In summary, the prognostic value of TB was retained regardless of whether TB counts in a 0.95 mm 2 field were normalized. Normalization resulted in overcorrecting TB counts with consequent downgrading of most borderline cases. This has implications for risk stratification and adjuvant treatment decisions, and suggests the need to re-evaluate the role of normalization in TB assessment.

Emerging evidence has demonstrated that tumour budding (TB) is negatively associated with T-lymphocyte infiltration in CRC. Despite extensive research, the molecular characteristics of immunologically 'hot' TB remain poorly understood.

We quantified the number of TB by haematoxylin-eosin (H&E) sections and the densities of CD3+ and CD8+ T-lymphocytes by immunohistochemistry in a CRC cohort of 351 cases who underwent curative resection. We analysed the differential expression and T-lymphocyte infiltration score of 37 human epithelial keratins in CRC using RNA sequencing from the TCGA dataset. In 278 TB-positive cases, KRT17 expression was evaluated in tumour centre (TC) and TB with a staining score. Patient demographic, clinicopathological features and survival rates were analysed.

In a CRC cohort of 351 cases, low-grade TB was associated with high CD3+ and CD8+ T-cell densities in the invasive margin (IM) but not in the TC. Of 37 human epithelial keratins, only KRT17 expression in TB had an apparent association with TB-grade and T-lymphocyte infiltration. In 278 TB-positive cases, high KRT17 expression in TB (KRT17TB) was negatively associated with low-grade TB and positively associated with high CD3+ and CD8+ T-cell densities in IM. High KRT17TB predicted early tumour grade, absence of lymph node metastasis and absence of tumour deposits. Additionally, patients with high KRT17TB had good overall survival and disease-free survival. Notably, low KRT17TB can specifically identify those patients with a poor prognosis among colorectal cancer patients with low TB and high T-lymphocyte infiltration.

KRT17 can be employed as a new indicator for distinguishing different immunological TBs.

Tumor budding (TB) has emerged as a promising independent prognostic biomarker in colorectal cancer (CRC). The prognostic role of TB has been extensively studied and currently affects clinical decision making in patients with stage I and II CRC. However, existing prognostic studies on TB in stage III CRC have been confined to small retrospective cohort studies. Consequently, this study investigated the correlation among TB categories, clinicopathological features, and prognosis in stage III-IV CRC to further enhance the precision and individualization of treatment through refined prognostic risk stratification.

To analyze the relationship between TB categories and clinicopathological characteristics and assess their prognostic value in stage III-IV CRC to further refine the prognostic risk stratification of stage III-IV CRC.

The clinical data of 547 CRC patients were collected for this retrospective study. Infiltration at the front edge of the tumor buds was counted according to the 2016 International Tumor Budding Consensus Conference guidelines.

Multivariate Cox proportional hazards regression analysis demonstrated that chemotherapy (P = 0.004), clinical stage IV (P < 0.001), ≥ 4 regional lymph node metastases (P = 0.004), left-sided colonic cancer (P = 0.040), and Bd 2-3 (P = 0.002) were independent prognostic factors in patients with stage III-IV CRC. Moreover, the density of tumor infiltrating lymphocytes was higher in Bd 1 than in Bd 2-3, both in the tumor stroma and its invasive margin.

TB has an independent predictive prognostic value in patients with stage III-IV CRC. It is recommended to complete the TB report of stage III-IV CRC cases in the standardized pathological report to further refine risk stratification.

We aimed to assess the efficacy of machine learning and radiomics analysis using magnetic resonance imaging (MRI) with a hepatospecific contrast agent, in a pre-surgical setting, to predict tumor budding in liver metastases.

Patients with MRI in a pre-surgical setting were retrospectively enrolled. Manual segmentation was made by means 3D Slicer image computing, and 851 radiomics features were extracted as median values using the PyRadiomics Python package. Balancing was performed and inter- and intraclass correlation coefficients were calculated to assess the between observer and within observer reproducibility of all radiomics extracted features. A Wilcoxon-Mann-Whitney nonparametric test and receiver operating characteristics (ROC) analysis were carried out. Balancing and feature selection procedures were performed. Linear and non-logistic regression models (LRM and NLRM) and different machine learning-based classifiers including decision tree (DT), k-nearest neighbor (KNN) and support vector machine (SVM) were considered.

The internal training set included 49 patients and 119 liver metastases. The validation cohort consisted of a total of 28 single lesion patients. The best single predictor to classify tumor budding was original_glcm_Idn obtained in the T1-W VIBE sequence arterial phase with an accuracy of 84%; wavelet_LLH_firstorder_10Percentile was obtained in the T1-W VIBE sequence portal phase with an accuracy of 92%; wavelet_HHL_glcm_MaximumProbability was obtained in the T1-W VIBE sequence hepatobiliary excretion phase with an accuracy of 88%; and wavelet_LLH_glcm_Imc1 was obtained in T2-W SPACE sequences with an accuracy of 88%. Considering the linear regression analysis, a statistically significant increase in accuracy to 96% was obtained using a linear weighted combination of 13 radiomic features extracted from the T1-W VIBE sequence arterial phase. Moreover, the best classifier was a KNN trained with the 13 radiomic features extracted from the arterial phase of the T1-W VIBE sequence, obtaining an accuracy of 95% and an AUC of 0.96. The validation set reached an accuracy of 94%, a sensitivity of 86% and a specificity of 95%.

Machine learning and radiomics analysis are promising tools in predicting tumor budding. Considering the linear regression analysis, there was a statistically significant increase in accuracy to 96% using a weighted linear combination of 13 radiomics features extracted from the arterial phase compared to a single radiomics feature.

Background: Endoscopic resection (ER) is a minimally invasive therapeutic approach for early gastric cancer (EGC), particularly for cases with a low risk of lymph node metastasis (LNM). Tumor budding (TB) has gained attention as a potential prognostic indicator for LNM in EGC. Case Presentation: We report two cases-a 73-year-old and an 81-year-old male patient-who presented with gastric adenocarcinoma. Both patients had small-sized, differentiated, and intramucosal adenocarcinomas. However, high-grade TBs per high-power field under ×200 magnification at the invasive front and LNMs were found in both cases. Conclusions: These cases conformed to the post-ER observation guidelines of the current treatment protocol, yet demonstrated LNMs. We found that TB could serve as an effective prognostic marker for LNM compared to traditional risk factors. The aim of this study is to re-examine the ability of TB to predict LNM in EGC, thereby providing an impetus for reconsideration and potential revision of the current treatment guidelines for EGC.

Current clinical guidelines recommend the removal of at least 12 lymph nodes (LNs) in resectable colorectal cancer (CRC). With advancements in lymphadenectomy technologies, the number of retrieved lymph nodes (rLNs) has markedly increased. This study aimed to investigate the lowest number of rLNs in node-negative patients.

A total of 1103 N0 and 208 N1a stage patients were enrolled in our cohort, while 8503 N0 and 1276 N1a patients from the Surveillance, Epidemiology, and End Results CRC database were included. Propensity score matching and multivariate Cox regression analyses were performed to mitigate the influence of selection bias and control for potential confounding variables.

The median number of rLNs in N0 patients increased from 13.5 (interquartile range [IQR]: 9-18) in 2013 to 17 (IQR: 15-20) in 2019. The restrictive cubic spline illustrated a nonlinear relationship between rLNs and prognosis (nonlinearity, P =0.009), with a threshold ( N =16) influencing clinical outcomes. Patients at either N0 or N1a stage with sufficient rLNs (≥16) demonstrated superior prognoses to those with a limited rLNs (<16). After adjusting for clinical confounders, similar prognoses were observed in N0 limited and N1a adequate populations. Furthermore, Kaplan-Meier curves revealed that N0 limited patients who received chemotherapy exhibited better outcomes than those who did not.

Among patients with node-negative CRC, it is crucial to remove 16 or more LNs effectively. Fewer than 16 rLNs should be regarded as an independent risk factor, implying the need for adjuvant chemotherapy.

In this study, we investigated the relationship between programmed cell death ligand 1 (PD-L1) and programmed cell death protein 1 (PD-1) expression in colon adenocarcinoma tumor budding.

This study included 122 patients with colon adenocarcinomas. The largest sample of formaldehyde-fixed paraffin-embedded tumor tissues was selected for analysis. Expression of membranous PD-L1 (clone 22C3) and the Combined Positive Score (CPS) in tumor tissues was calculated and graded according to the percentages of peritumoral and intratumoral tumor cells (0 %, 1 %, 1-5 %, >5 %). The effects of these factors on the prognosis were analyzed.

Tumor budding was associated with adverse clinicopathological features and poor overall survival. PD-L1 (CPS%) peritumoral tumor budding (1 %/<1 %) was statistically significant in the univariate model (p = 0.004). Age, organ metastases (liver, lung, liver, lung, and peritoneum), and metastases were statistically significant in the multivariate model (p = 0.001, p = 0.004, p = 0.001, p = 0.002, p = 0.004, and p = 0.032, respectively). PD-L1 positive staining was mostly observed around the tumor and during tumor budding. PD-L1 peritumoral tumor budding rates and patients' survival rates differed significantly (log-rank = 12.07, p = 0.007).

We found that patients with PD-L1 (CPS%) > 1 % in tumor budding had a shortened life expectancy and demonstrated the importance of including tumor budding areas in the samples used for biomarker evaluation. We previously reported that PD-L1 expression in tumor budding is associated with more aggressive cancer biology and poor survival, although overall survival is of limited statistical significance.

Neoadjuvant chemoradiotherapy (CRT) is the standard treatment for advanced rectal cancer. Yet, the response to CRT varies from complete response to zero tumor regression.

The impact of intratumoral budding (ITB) and intratumoral CD8+ cell density on response to CRT and survival were evaluated in biopsy samples from 266 patients with advanced rectal cancer who were treated with long-course neoadjuvant CRT. The expression of epithelial-mesenchymal transition (EMT) markers was compared between patients with high and low ITB, using data from 174 patients with RNA sequencing.

High ITB was observed in 62 patients (23.3%). There was no association between ITB and CD8+ cell density. The multivariable logistic regression analysis showed that high CD8+ cell density (OR, 2.69; 95% CI, 1.45-4.98; P = .002) was associated with good response to CRT, whereas high ITB (OR, 0.33; 95% CI, 0.14-0.80; P = .014) was associated with poor response. Multivariable Cox regression analysis for survival showed that high CD8+ cell density was associated with better recurrence-free survival (HR, 0.41; 95% CI, 0.24-0.72; P = .002) and overall survival (HR, 0.36; 95% CI, 0.17-0.74; P = .005), but significance values for ITB were marginal (P = .104 for recurrence-free survival and P = .163 for overall survival). The expression of EMT-related genes was not significantly different between patients with high and low ITB.

ITB and CD8+ cell density in biopsy samples may serve as useful biomarkers to predict therapy response in patients with rectal cancer treated with neoadjuvant CRT.

Tumour budding has been recognized as a morphologic marker of tumour invasion. Invasive characteristics such as depth of invasion, mode of invasion and worst pattern of invasion are potentially powerful parameters predicting the regional metastasis.

This study was done to understand the significance of tumour budding and various characteristics of invasion and their impact on grading of oral squamous cell carcinoma.

An immunohistochemical study was performed on tissue sections obtained from 34 paraffin-embedded blocks of clinically and histologically diagnosed cases of oral squamous cell carcinoma. The sections were stained with pan cytokeratin and observed under high power magnification.

Tumour budding and the invasive patterns were found to be significant in OSCC. A proposed grading system based on tumour budding and cell nest was found to have a significant correlation with the WHO grading system.

This study demonstrated the importance of using tumour buds as an additional parameter in the grading system and also assessed the importance of invasive patterns, cellular atypia and stromal contents in OSCC.

Head and neck squamous cell carcinoma forms an anatomically and functionally complex group of malignancies. The significant local aggressiveness and frequent regional relapses motivate ongoing research to identify more reliable and sensitive prognostic and predictive biomarkers. One emerging area of cancer biology is the evaluation of tumor budding at the advancing invasive front of various types of epithelial cancers. Recent studies suggest that tumor budding is a relatively common phenomenon in cancer progression and that it may have important prognostic implications for patients due to its potential to provide valuable insights into the biology and clinical behavior of head and neck cancer. In this review, we aim to provide information about tumor budding in head and neck squamous cell carcinoma. Thus, we hope to shed light on the complex biology of these malignancies, as well as aiding diagnostic, classification, and better characterization and thereby, looking for new avenues for improving patient outcomes.