• chemotherapy
• conversion surgery
• gastric mixed adenoneuroendocrine carcinoma
• immunotherapy
• targeted therapy

• colorectal cancer
• combined modality therapy
• immune checkpoint inhibitors
• immunotherapy
• microsatellite stabilization

• Humans
• Colorectal Neoplasms/immunology
• Colorectal Neoplasms/therapy
• Colorectal Neoplasms/drug therapy
• Colorectal Neoplasms/genetics
• Immune Checkpoint Inhibitors/therapeutic use
• Immune Checkpoint Inhibitors/pharmacology
• Microsatellite Instability
• Programmed Cell Death 1 Receptor/antagonists & inhibitors
• Programmed Cell Death 1 Receptor/immunology
• Programmed Cell Death 1 Receptor/metabolism
• Immunotherapy/methods
• B7-H1 Antigen/antagonists & inhibitors
• B7-H1 Antigen/metabolism
• Tumor Microenvironment/immunology
• Animals
• Combined Modality Therapy

• YYGL202228 Hospital Level Management Project of Subei People's Hospital
• No.YZ2021075 the Social Development-Health Care Project of Yangzhou, Jiangsu Province

• CRC
• DFS
• MSI
• OS
• Prognosis

• Mice
• Animals
• Humans
• Receptor, Transforming Growth Factor-beta Type II/genetics
• Receptors, Transforming Growth Factor beta/genetics
• Receptors, Transforming Growth Factor beta/metabolism
• Protein Serine-Threonine Kinases/metabolism
• Heterografts
• Lentivirus/metabolism
• Transforming Growth Factor beta/metabolism
• Cell Line
• Neoplasms

• PIP 2013 GI, 11220120100202CO Consejo Nacional de Investigaciones Científicas y Técnicas (National Scientific and Technical Research Council)
• PIP 2017 528 GI, 11220170100573CO Consejo Nacional de Investigaciones Científicas y Técnicas (National Scientific and Technical Research Council)
• PICT-2020-SERIE A-03635 Ministry of Science, Technology and Productive Innovation, Argentina | Agencia Nacional de Promoción Científica y Tecnológica (National Agency for Science and Technology, Argentina)

• microsatellite instability
• tumor-only
• colorectal cancer
• next-generation sequencing
• dna mismatch repair

• Humans
• Microsatellite Instability
• Colorectal Neoplasms/diagnosis
• Microsatellite Repeats/genetics
• DNA Mismatch Repair

• WDR12
• expression
• immunotherapy
• pan-cancer
• prognosis

Background: Homeostasis of proliferating tissues is strongly dependent on intact DNA. Both neoplastic and non-neoplastic diseases have been associated with MSH2 (MutS homolog 2, a mismatch repair protein) deficiency. In this study, we examined how age and diabetes mellitus influence the expression of MSH2 in the kidney. Methods: To study the effect of age, three groups of healthy rats were formed: 2 months, 8 months, and 14 months old. Two groups of diabetic rats were formed: 8 months old and 14 months old. Expression of MSH2 in the kidney was studied by quantifying immunofluorescent staining. Results: Age was identified as the main factor that influences MSH2 expression in kidneys. The effect of age followed parabolic dynamics, with peak expression at 8 months of age and similar levels at 2 and 14 months. Diabetes had an age-dependent effect, which manifested as the increase of MSH2 expression in 14-month-old diabetic rats in comparison to healthy animals. Conclusions: Age influences MSH2 expression in the kidney more than diabetes mellitus. Since ageing is a risk factor for kidney neoplasia, downregulation of MSH2 in older rats might represent one of the pro-oncogenic mechanisms of ageing at a molecular level.

• MSH2
• diabetes mellitus
• kidney

• Aging
• Animals
• Diabetes Mellitus, Experimental/genetics
• Diabetes Mellitus, Type 1/genetics
• Down-Regulation
• Kidney/metabolism
• MutS Homolog 2 Protein/genetics
• Proteins/genetics
• Rats

• ICI combination therapy
• colorectal cancer
• immune checkpoint inhibitors
• immunotherapy
• microsatellite

• MSI
• cfDNA
• ctDNA
• machine learning

• Circulating Tumor DNA/blood
• Circulating Tumor DNA/genetics
• Computational Biology/methods
• High-Throughput Nucleotide Sequencing/statistics & numerical data
• Humans
• Limit of Detection
• Machine Learning
• Microsatellite Instability
• Microsatellite Repeats
• Neoplasms/blood
• Neoplasms/diagnosis
• Neoplasms/genetics
• Neoplasms/pathology
• Sequence Analysis, DNA
• Software

• National Natural Science Foundation of China
• Chinese Academy of Sciences

• C3
• Colorectal adenocarcinoma
• Immune cell
• Immunotherapy
• TCGA
• Tumor microenvironment

• Adenocarcinoma/genetics
• Adenocarcinoma/immunology
• Adenocarcinoma/mortality
• Adenocarcinoma/therapy
• Adult
• Aged
• Aged, 80 and over
• Colorectal Neoplasms/genetics
• Colorectal Neoplasms/immunology
• Colorectal Neoplasms/mortality
• Colorectal Neoplasms/therapy
• Complement C3/genetics
• Databases, Genetic
• Female
• Gene Expression/immunology
• Humans
• Immunity, Cellular
• Immunotherapy
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Prognosis
• Proportional Hazards Models
• Protein Interaction Maps
• Sequence Analysis, RNA
• Statistics, Nonparametric
• Tumor Microenvironment/genetics
• Tumor Microenvironment/immunology

Mismatch repair (MMR)/microsatellite instability (MSI) and tumor mutational burden (TMB) are independent biomarkers that complement each other for predicting immune checkpoint inhibitors (ICIs) efficacy. Here we aim to establish a strategy that integrates MSI and TMB determination for colorectal cancer (CRC) in one single assay.

Surgical or biopsy specimens retrospectively collected from CRC patients were subjected to NGS analysis. Immunohistochemistry (IHC) and polymerase chain reaction (PCR) were also used to determine MMR/MSI for those having enough tissues. The NGS-MSI method was validated against IHC and PCR. The MSI-high (MSI-H) or microsatellite stable (MSS) groups were further stratified based on tumor mutational burden, followed by validation using the The Cancer Genome Atlas (TCGA) CRC dataset. Immune microenvironment was evaluated for each subgroup be profiling the expression of immune signatures.

Tissues from 430 CRC patients were analyzed using a 381-gene NGS panel. Alterations in KRAS, NRAS, BRAF, and HER2 occurred at a significantly higher incidence among MSI-H tumors than in MSS patients (83.6% vs. 58.4%, p = 0.0003). A subset comprising 98 tumors were tested for MSI/MMR using all three techniques, where NGS proved to be 99.0 and 93.9% concordant with PCR and IHC, respectively. Four of the 7 IHC-PCR discordant cases had low TMB (1.1–8.1 muts/Mb) and were confirmed to have been misdiagnosed by IHC. Intriguingly, 4 of the 66 MSS tumors (as determined by NGS) were defined as TMB-high (TMB-H) using a cut-off of 29 mut/Mb. Likewise, 15 of the 456 MSS tumors in the TCGA CRC cohort were also TMB-H with a cut-off of 9 muts/Mb. Expression of immune signatures across subgroups (MSS-TMB-H, MSI-H-TMB-H, and MSS-TMB-L) confirmed that the microenvironment of the MSS-TMB-H tumors was similar to that of the MSI-H-TMB-H tumors, but significantly more immune-responsive than that of the MSS-TMB-L tumors, indicating that MSI combined with TMB may be more precise than MSI alone for immune microenvironment prediction.

This study demonstrated that NGS panel-based method is both robust and tissue-efficient for comprehensive molecular diagnosis of CRC. It also underscores the importance of combining MSI and TMB information for discerning patients with different microenvironment.

The online version contains supplementary material available at 10.1186/s12885-021-07942-1.

• Colorectal cancer
• Immune checkpoint inhibitor
• Microsatellite instability
• Next generation sequencing
• Tumor mutation burden

• colorectal cancer
• immunohistochemistry
• microsatellite instability
• mismatch repair
• polymerase chain reaction-capillary electrophoresis

• Colon cancer
• Consensus molecular subtypes
• Genomic classification
• Transcriptomic classification

With the recent emergence of immune checkpoint inhibitors, microsatellite instability (MSI) status has become an important biomarker for immune checkpoint blockade therapy. There are growing technical demands for the integration of different genomic alterations profiling including MSI analysis in a single assay for full use of the limited tissues.

Tumor and paired control samples from 64 patients with primary colorectal cancer were enrolled in this study, including 14 MSI-high (MSI-H) cases and 50 microsatellite stable (MSS) cases determined by MSI-PCR. All the samples were sequenced by a customized NGS panel covering 2.2 MB. A training dataset of 28 samples was used for selection of microsatellite loci and a novel NGS-based MSI status classifier, USCI-msi, was developed. NGS-based MSI status, single nucleotide variant (SNV) and tumor mutation burden (TMB) were detected for all patients. Most of the patients were also independently detected by immunohistochemistry (IHC) staining.

A 9-loci model for detecting microsatellite instability was able to correctly predict MSI status with 100% sensitivity and specificity compared with MSI-PCR, and 84.3% overall concordance with IHC staining. Mutations in cancer driver genes (APC, TP53, and KRAS) were dispersed in MSI-H and MSS cases, while BRAF p.V600E and frameshifts in TCF7L2 gene occurred only in MSI-H cases. Mismatch repair (MMR)-related genes are highly mutated in MSI-H samples.

We established a new NGS-based MSI classifier, USCI-msi, with as few as 9 microsatellite loci for detecting MSI status in CRC cases. This approach possesses 100% sensitivity and specificity, and performed robustly in samples with low tumor purity.

• BRAF
• Colorectal cancer (CRC)
• Immunotherapy
• KRAS
• Microsatellite instability (MSI)
• Mismatch repair
• NGS
• TCF7L2

• cancer prevention
• cancer therapy
• colon cancer
• immunogenic cell death

• Colorectal neoplasms
• Pathology report
• Protocol
• Standardization

• Colorectal cancer
• M1 stage
• Nomogram
• SEER

Worldwide, neoplasms of the gastrointestinal tract have a very high incidence and mortality. Among these, colorectal cancer, which includes colon and rectum malignancies, representing both highest incidence and mortality. While gallbladder cancer, another neoplasm associated to gastrointestinal tract occurs less frequently. Genetic factors, inflammation and nutrition are important risk factors associated with colorectal cancer development. Likewise, pathogenic microorganisms inducing intestinal dysbiosis have become an important scope to determine the role of bacterial infection on tumorigenesis. Interestingly, in human biopsies of different types of gastrointestinal tract cancer, the presence of different bacterial strains, such as Fusobacterium nucleatum, Escherichia coli, Bacteroides fragilis and Salmonella enterica have been detected, and it has been considered as a high-risk factor to cancer development. Therefore, pathogens infection could contribute to neoplastic development through different mechanisms; including intestinal dysbiosis, inflammation, evasion of tumoral immune response and activation of pro-tumoral signaling pathways, such as β catenin. Here, we have reviewed the suggested bacterial molecular mechanisms and their possible role on development and progression of gastrointestinal neoplasms, focusing mainly on colon neoplasms, where the bacteria Fusobacterium nucleatum, Escherichia coli, Bacteroides fragilis and Salmonella enterica infect.

• Colorectal cancer
• Immunohistochemistry
• Mismatch repair proteins
• Sudan

• Chromosomal instability
• Colorectal carcinoma
• Microsatellite instability
• Pakistan

• Colorectal cancer
• DNA mismatch repair
• DNA polymerase epsilon
• Endometrial cancer
• Immune checkpoint inhibitor
• Immune signature
• Immunotherapy
• Microsatellite instability
• Neoantigen

Microsatellite instability (MSI) operates as the second major pathway in the colorectal carcinogenesis. Although genetic testing remains the gold standard for the detection of MSI, the College of American Pathologists (CAP) recommends an initial immunohistochemical workup with a four-antibody panel (MLH1, PMS2, MSH2, and MSH6) to screen for a defective mismatch repair system. An increased trend towards young age colorectal carcinoma (CRC) has been noticed in our population over recent years; however, neither screening for MSI by immunohistochemistry (IHC)/genetic testing was done nor were its morphological features studied. We aimed to determine the frequency of mismatch repair deficiency (dMMR) by loss of IHC expression of the aforementioned enzymes in CRC patients and its correlatation with clinicopathologic parameters.

This was a retrospective study conducted at Liaquat National Hospital, Karachi, between 2012 and 2015. A total of 100 cases of CRC were included in the study that underwent surgical resection. IHC stains using antibodies MLH1, PMS2, MSH2, and MSH6 were performed by DAKO EnVision method on representative tissue blocks. The results were interpreted by senior histopathologists and correlated with clinico-pathological parameters.

A total of 100 cases of CRC were studied that included 51 males and 49 females. Thirty-four percent (n = 34) of the patients showed loss of IHC staining for MMR markers. Combined loss of expression for MLH1/PMS2 were observed in 16% (n = 16) of the cases. Loss of MSH2/MSH6 were seen in 6% (n = 6) of the cases. Loss of expression for all markers were noted in 7% (n = 7) of the cases. There were 5% (n = 5) of the cases that showed isolated loss of MLH1 only. The tumors with dMMR status were significantly associated with right-sided location (p = 0.013), exhibited intra-tumoral lymphocytosis (p = 0.007), and lymphovascular invasion (p = 0.043). No significant association was seen with gender, age, tumor stage, grade, or other morphological features.

The frequency of mismatch repair deficiency in CRC patients was found to be 34% in Pakistani population which warrants further genetic testing to exclude Lynch syndrome. Moreover, right-sided location and intra-tumoral lymphocyte count may be used to identify patients who may need further workup.

• Colon
• Immunohistochemistry
• Microsatellite instability
• Mismatch repair deficiency
• TILs

• Colorectal cancer
• Immunotherapy
• Lynch
• Microsatellite instability
• Mismatch-repair

• Colorectal cancer
• mismatch repair deficiency
• reflex immunohistochemistry
• screening

Recent studies have reported increased mortality for right-sided colon cancers; however, the results are conflicting for different stage tumors. We examined the differences in clinicopathology between right- and left-sided colon cancers and the relationships between colon cancer location (right- and left-side) and 5-year disease-free survival (DFS) and overall survival (OS).

We identified patients from 2005 to 2008 with stage II/III colon cancer who underwent surgery for curative intent. We explored the impact of the tumor location on the postoperative DFS and OS using univariate and multivariate analyses.

Of 627 patients, 50.6% (317/627) had right-sided colon cancer. These patients were more likely to have weight loss, second primary tumor, elevated preoperative carbohydrate antigen 19-9 (CA19-9), increased incidence of non-adenocarcinoma, more poorly differentiated tumors, vascular invasion, defective mismatch repair, and a lighter smoking history (P < 0.05). Right-sided colon cancer had a higher recurrence incidence compared with left-sided cancer (30.6% vs. 23.2%, P = 0.037), particularly with multiple metastatic sites in the first recurrence (17.5% vs. 5.6%, P = 0.020). Kaplan–Meier survival curves demonstrated a significant difference in the 5-year DFS rate between right- and left-sided cancers across all stages (68.1% vs. 75.2%, P = 0.043). However, there was no significant difference in the 5-year OS rate between the two groups (73.8% vs. 79.0%, P = 0.103). Subgroup analysis demonstrated that patients with left-sided colon cancer had a significantly better 5-year DFS and OS rates compared with those with right-sided disease at stage III (64.3% vs. 46.8%, P = 0.002; 69.5% vs. 53.5%, P = 0.006, respectively); there were no significant differences in the 5-year DFS and OS rates at stage II (85.2% vs. 85.9%, P = 0.819; 89.8% vs. 88.5%, P = 0.803, respectively). Adjusted Cox regression analysis showed no significant differences in the 5-year OS and DFS rates for stage II [hazard ratio (HR) = 1.203, 95% confidence interval (CI): 0.605–2.391, P = 0.598; HR = 0.980, 95% CI: 0.542–1.774, P = 0.948, respectively] or all stages combined (HR = 0.867, 95% CI: 0.613–1.227, P = 0.421; HR = 0.832, 95% CI: 0.606–1.142, P = 0.255, respectively). However, stage III left-sided cancer had higher 5-year OS and DFS rates (HR = 0.626, 95% CI: 0.414–0.948, P = 0.027; HR = 0.630, 95% CI: 0.428–0.926, P = 0.019, respectively).

We found that right- and left-sided colon cancers had significantly different clinicopathological characteristics. Right-sided colon cancer had a higher incidence of recurrence than left-sided disease. Patients with stage III right-sided colon cancer had a worse prognosis compared with those with stage III left-sided colon cancer.

• Colon cancer
• Location
• Recurrence
• Survival

Colorectal cancer belongs to the most frequent occurring malignancies. A prediction of the clinical outcome and appropriate choice of neoadjuvant chemotherapy needs personalized insight to the main driving pathways. Because most CRCs have polyps as progenitor lesions, studying the pathways driving to adenomagenesis is no less important.

Our purpose was the evaluation of microsatellite stability status within conventional colon adenomas and also β-catenin, BRAFV600E and p53 contribution.

The cohort included 101 cases of typical colon adenomas with high grade epithelial dysplasia according to WHO. An immunohistochemistry method was used for the depiction of the expression of targeted proteins, as also their heterogeneity.

Generally, we noted a 10% frequency of MSI events where MSI-H reached a 5% share occurred within the left colon and rectal polyps. β-catenin nuclear overexpression was noted with a 70% frequency and p53 with close to a 24% frequency. In addition, we found a presence of micro-serration foci more often within tubular adenomas, where focal MSI took place more often. Our results indicate that MSI events occur more often than had been theorized earlier. It results in tumour heterogeneity, more complex underlying pathways and finally ontogenetic molecular-diversity of tumours besides similar occurring histopathological features.

• Adenoma/genetics
• Adenoma/pathology
• Adult
• Aged
• Aged, 80 and over
• Colonic Polyps/genetics
• Colonic Polyps/pathology
• Colorectal Neoplasms/genetics
• Colorectal Neoplasms/pathology
• DNA Methylation/genetics
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Male
• Microsatellite Instability
• Middle Aged
• Mutation
• Proto-Oncogene Proteins B-raf/genetics
• Tumor Suppressor Protein p53/genetics
• beta Catenin/biosynthesis
• beta Catenin/genetics

• Jan Kochanowski University in Kielce, Poland.

• Colorectal cancer
• Metastasis
• Prognosis
• Serum markers
• Tissue markers

To evaluate the Recurrence Score^® of the quantitative 12-multigene expression assay and to determine risk groups based on the continuous Recurrence Score^® in Korean patients.

A total of 95 patients with pathological T3N0 tumors and mismatch repair-proficient tumors were enrolled. The Recurrence Score^® was used to classify risk groups (low risk, <30; intermediate risk, 30–40; high risk, ≥41).

Fifty-four patients (56.8%) were aged over 70 years. There were 49 men (51.6%) and 56 cases of right-sided colon cancer (58.9%). Eight cases (8.4%) had well-differentiated tumors, and 86 cases (90.5%) showed moderate differentiation. Only one case (1.1%) had a poorly differentiated tumor. Three patients (3.2%) had lymphovascular invasion. Sixty-one patients were identified as low risk (64.2%) and 34 patients as intermediate risk (35.8%). There were no high-risk patients. Although not significant, the 3-year recurrence risk increased with the Recurrence Score^®.

Distribution patterns of risk groups based on the Recurrence Score^®, particularly the absence of a high-risk group, were different from the prior validation studies. These findings suggest that ethnic differences between Koreans and Western patients are potential contributing factors for different gene expressions in the quantitative 12-multigene expression assay.

• adjuvant chemotherapy
• colonic neoplasms
• ethnic groups
• gene expression

• Colorectal cancer
• Lynch syndrome
• Mismatch repair gene

• Adult
• Age Factors
• Biomarkers/analysis
• Colorectal Neoplasms, Hereditary Nonpolyposis/diagnosis
• Colorectal Neoplasms, Hereditary Nonpolyposis/epidemiology
• Colorectal Neoplasms, Hereditary Nonpolyposis/genetics
• Colorectal Neoplasms, Hereditary Nonpolyposis/surgery
• DNA Methylation
• DNA Mismatch Repair/genetics
• Female
• Genetic Testing
• Hospitals/statistics & numerical data
• Humans
• Japan/epidemiology
• Male
• Microsatellite Instability
• Middle Aged
• MutL Protein Homolog 1/analysis
• MutL Protein Homolog 1/genetics
• Mutation
• Prevalence
• Promoter Regions, Genetic
• Proto-Oncogene Proteins B-raf/genetics

• 5-Fluorouracil
• Colon cancer
• Irinotecan
• Mismatch repair gene
• Thymidylate synthase

Recent studies have revealed that a small subset of Lynch syndrome-associated colorectal carcinomas (CRCs) is caused by a germline EPCAM deletion-induced MSH2 epimutation. Based on the finding of this genetic alteration, we investigated the implications of EPCAM expression changes in microsatellite instability-high (MSI-H) CRCs.

Expression of EPCAM and DNA mismatch repair proteins was assessed by immunohistochemistry in 168 MSI-H CRCs. Using DNA samples of these tumors, MLH1 promoter methylation status was also determined by methylation-specific real-time polymerase chain reaction method (MethyLight).

Among 168 MSI-H CRCs, complete loss (CL) and focal loss (FL) of EPCAM expression was observed in two (1.2%) and 22 (13.1%) cases, respectively. Both of the EPCAM-CL cases were found in MSH2-negative tumors without MLH1 promoter methylation. However, only nine of the 22 EPCAM-FL tumors had MSH2 deficiency. Of the 22 EPCAM-FL tumors, 13 showed MLH1 loss, and among them, nine cases were determined to have MLH1 methylation. EPCAM-FL was significantly associated with advanced stage (p=.043), distant metastasis (p=.003), poor differentiation (p=.001), and signet ring cell component (p=.004).

Loss of EPCAM expression is differentially associated with clinicopathological and molecular features, depending on the completeness of the loss, in MSI-H CRCs.

• Colorectal neoplasms
• DNA mismatch repair
• EPCAM
• Microsatellite instability

• PD-1
• PD-L1
• checkpoint blockade
• epigenetics
• immune evasion
• immunotherapy

Colorectal cancers (CRCs) with a high level of microsatellite instability (MSI-H) are clinicopathologically distinct tumors characterized by predominance in females, proximal colonic localization, poor differentiation, mucinous histology, tumor-infiltrating lymphocytes, a Crohn’s-like lymphoid reaction and a favorable prognosis. In terms of their molecular features, MSI-H CRCs are heterogeneous tumors associated with various genetic and epigenetic alterations, including DNA mismatch repair deficiency, target microsatellite mutations, BRAF mutations, a CpG island methylator phenotype-high (CIMP-H) status, and a low level of genomic hypomethylation. The molecular heterogeneity of MSI-H CRCs also depends on ethnic differences; for example, in Eastern Asian countries, relatively low frequencies of CIMP-H and BRAF mutations have been observed in MSI-H CRCs compared to Western countries. Although the prognostic features of MSI-H CRCs include a favorable survival of patients and low benefit of adjuvant chemotherapy, there may be prognostic differences based on the molecular heterogeneity of MSI-H CRCs. Here, we have reviewed and discussed the molecular and prognostic features of MSI-H CRCs, as well as several putative prognostic or predictive molecular markers, including HSP110 expression, beta2-microglobulin mutations, myosin 1a expression, CDX2/CK20 expression, SMAD4 expression, CIMP status and LINE-1 methylation levels.

• Colorectal cancer
• Microsatellite instability
• DNA mismatch repair
• DNA methylation
• CpG islands
• Prognosis
• Adjuvant chemotherapy

• CDX2 Transcription Factor
• Cell Differentiation
• Colorectal Neoplasms/genetics
• Colorectal Neoplasms/metabolism
• CpG Islands
• DNA Methylation
• DNA Repair
• Epigenesis, Genetic
• Gene Expression Regulation, Neoplastic
• Germ-Line Mutation
• Homeodomain Proteins/metabolism
• Humans
• Long Interspersed Nucleotide Elements/genetics
• Microsatellite Instability
• Microsatellite Repeats/genetics
• Mutation
• Phenotype
• Prognosis
• Proto-Oncogene Proteins/metabolism
• Proto-Oncogene Proteins B-raf/metabolism
• Proto-Oncogene Proteins p21(ras)
• Smad4 Protein/metabolism
• Treatment Outcome
• ras Proteins/metabolism

Rhabdoid colorectal carcinomas are very rare and only 10 cases have been previously reported. We report two cases of rhabdoid colorectal carcinoma, one arising in the sigmoid colon of a 62-year-old man and another in the rectum of an 83-year-old woman. In both cases, the patients had advanced tumors with lymph node metastases. The tumors mostly showed a diffuse arrangement with rhabdoid features and small glandular regions were combined. Transitional areas from the adenocarcinomas to the rhabdoid tumors were also noted. Adenocarcinoma cells were positive for mixed cytokeratin (CK), CK20 and epithelial membranous antigen (EMA), but focal positive for vimentin. The rhabdoid tumor cells were positive for mixed CK, but focal positive or negative for CK20 and EMA. In addition, they were diffusely positive for vimentin, but negative for desmin. The histological and immunohistologial findings of these two cases suggest that the rhabodid tumor cells originated from dedifferentiated adenocarcinomas.

• Adenocarcinoma
• Colon
• Rectum
• Rhabdoid tumor

• Bak
• Bax
• histone deacetylase inhibitor
• romidepsin
• vorinostat

Colorectal cancer (CRC) incidence and mortality are constantly decreasing, but CRC still remains the third most prevalent cancer and the third most common cause of cancer death in both males and females in the United States. Recent rapid declines in CRC incidence rates have largely been attributed to increases in screening that can detect and remove precancerous polyps, and the decrease in death rates for CRC largely reflects improvements in early detection, treatment and the understanding of molecular/genetic basis of CRC. One of the important molecular/genetic findings is the presence of microsatellite instability (MSI) in CRCs. Many studies have shown the importance of MSI testing in diagnosing Lynch syndrome and predicting prognosis and response to chemotherapeutic agents in CRCs. Increased emphasis has been placed on the importance of MSI testing for all newly diagnosed individuals with CRCs. Both immunohistochemical staining (IHC) and polymerase chain reaction (PCR)-based MSI testing show high sensitivity and specificity in detecting MSI. The current clinical guidelines and histopathology features are indicative of, but not reliable in diagnosing Lynch syndrome and CRCs with MSI. Currently, there are evidences that universal testing for MSI starting with either IHC or PCR-based MSI testing is cost effective, sensitive, specific and is getting widely accepted.

• Colorectal cancer
• Lynch syndrome
• Universal testing
• DNA mismatch repair
• Microsatellite instability