• Computed tomography
• Deep learning
• Gastric cancer
• Radiomics

• HER2 expression
• gastric cancer
• pembrolizumab

• Efficacy index
• Lower perigastric lymph node
• Lymph node metastases
• Risk factors

• Humans
• Esophagogastric Junction/pathology
• Adenocarcinoma/surgery
• Adenocarcinoma/pathology
• Male
• Female
• Retrospective Studies
• Lymphatic Metastasis
• Middle Aged
• Stomach Neoplasms/pathology
• Stomach Neoplasms/surgery
• Risk Factors
• Gastrectomy/methods
• Aged
• Lymph Node Excision
• Esophageal Neoplasms/pathology
• Esophageal Neoplasms/surgery
• Adult
• Lymph Nodes/pathology
• Clinical Relevance

• nos. 82171720 National Natural Science Foundation of China
• nos. 82173218 National Natural Science Foundation of China
• no.5202008 Beijing Natural Science Foundation
• ZYLX202116 Beijing Hospitals Authority Clinical Medicine Development of Special Funding Support
• QNJJ2022019 Clinical Research Fund For Distinguished Young Scholars of Beijing Cancer Hospital

• Lauren classification
• contrast-enhanced computed tomography
• gastric cancer
• lymphovascular invasion
• radiomics

• Humans
• Stomach Neoplasms/diagnostic imaging
• Stomach Neoplasms/surgery
• Stomach Neoplasms/pathology
• Retrospective Studies
• Tomography, X-Ray Computed/methods
• Lymphatic Metastasis
• Contrast Media

• Belgian Shepherd dog
• Groenendael
• Tervueren
• canine
• carcinoma
• pathology
• stomach

• Cancer
• HER2
• Inhibitor
• Resistance

• Female
• Humans
• Breast Neoplasms/drug therapy
• Drug Resistance, Neoplasm
• Molecular Targeted Therapy/methods
• Signal Transduction

• SEER
• cancer-directed surgery
• gastric cancer
• overall survival rate
• stage IV

• fluorescence in situ hybridization
• gastric cancer
• human epidermal growth factor receptor 2
• lauren classification
• p53

• Humans
• Immunohistochemistry
• In Situ Hybridization, Fluorescence
• Receptor, ErbB-2/metabolism
• Stomach Neoplasms
• Tumor Suppressor Protein p53/metabolism

Gastric cancers (GCs) that express human erb-b2 receptor tyrosine kinase 2 (ERBB2, also known as HER2) account for 7.3%–20.2% of GCs. The pathological and prognostic factors associated with lymph node metastasis of such tumors are still unclear. Therefore, we aimed to identify the risk factors for lymph node metastasis and prognostic factors of patients with ERBB2-positive GC. We conducted a retrospective analysis of pathological specimens after D2 radical surgery for locally advanced GC and D1+ surgery performed for early GC in our hospital from January 2015 to December 2018. Patients with ERBB2-positive GC were selected and the potential risk factors for lymph node metastasis and potential factors affecting prognosis were evaluated. Among 1,124 GC patients, 122 diagnosed with ERBB2-positive GC were included in the study. We found that risk factors for lymph node metastasis included tumor size (hazard ratio (HR)- 6.213, 95% confidence interval (CI)- 2.097–18.407, p = 0.001), neural invasion (HR- 2.876, 95% CI - 1.011–8.184, p = 0.048), and vascular invasion (HR- 16.881, 95% CI - 5.207–54.727, p < 0.001). T stage (HR- 4.615, 95% CI - 2.182–9.759, p < 0.001) and vascular invasion (HR- 3.036, 95% CI - 1.369–6.736, p = 0.006) were significant prognostic variables. These findings shed new light on the pathology and prognosis of patients with ERBB2-positive GC.

While the incidence of gastric cancer (GC) in general has decreased worldwide in recent decades, the incidence of diffuse cancer historically comprising poorly cohesive cells-GC (PCC-GC) and including signet ring cell cancer is rising. Literature concerning PCC-GC is scarce and unclear, mostly due to a large variety of historically used definitions and classifications. Compared to other histological subtypes of GC, PCC-GC is nevertheless characterized by a distinct set of epidemiological, histological and clinical features which require a specific diagnostic and therapeutic approach. The aim of this review was to provide an update on the definition, classification and therapeutic strategies of PCC-GC. We focus on the updated histological definition of PCC-GC, along with its implications on future treatment strategies and study design. Also, specific considerations in the diagnostic management are discussed. Finally, the impact of some recent developments in the therapeutic management of GC in general such as the recently validated taxane-based regimens (5-Fluorouracil, leucovorin, oxaliplatin and docetaxel), the use of hyperthermic intraperitoneal chemotherapy as well as pressurized intraperitoneal aerosol chemotherapy and targeted therapy have been reviewed in depth for their relative importance for PCC-GC in particular.

• Poorly cohesive cells gastric carcinoma
• Review
• Definition
• Classification
• Therapeutic management

The Lauren classification of gastric tumors strongly correlates with prognosis. The purpose of this study was to explore the specific molecular mechanism of Lauren classification of gastric cancer and provide a possible theoretical basis for the treatment of gastric cancer.

We standardized the gene expression data of five Gene Expression Omnibus gastric cancer databases and constructed a Weighted Co-expression Network Analysis (WGCNA) model based on clinicopathological information. The overall survival (OS) and disease-free survival (DFS) curves were extracted from the Cancer Genome Atlas (TCGA) and GSE62254 databases. Western blotting was used to measure protein expression in cells and tissues. Scratch and transwell experiments were used to test the migration ability of tumor cells. Immunohistochemistry was used to measure tissue protein expression in clinical tissue samples to correlate to survival data.

The WGCNA model demonstrated that blue cyan was highly correlated with the Lauren classification of the tumor (r = 0.24, P = 7 × 10¹⁶). A protein-protein interaction network was used to visualize the genes in the blue cyan module. The OS and PFS TCGA analysis revealed that LMOD1 was a gene of interest. The proportion of diffuse gastric cancer patients with high expression of LMOD1 was significantly higher than that of intestinal type patients. LMOD1 promoted the migration of gastric cancer cells by regulating the FAK-Akt/mTOR pathway in vitro. Additionally, a Gene Set Enrichment Analysis using the TCGA and GSE62254 databases, and western blot data, showed that LMOD1 could promote an epithelial-mesenchymal transition (EMT), thus potentially affecting the occurrence of peritoneal metastasis of gastric cancer. Immunohistochemistry showed that LMOD1 was highly expressed in cancer tissues, and the prognosis of patients with high LMOD1 expression was poor.

LMOD1 is an oncogene associated with diffuse gastric cancer and can affect the occurrence and development of EMT by regulating the FAK-Akt/mTOR pathway. LMOD1 can therefore promote peritoneal metastasis of gastric cancer cells and can be used as a novel therapeutic target for gastric cancer.

The online version contains supplementary material available at 10.1186/s12885-022-09541-0.

• FAK-Akt/mTOR
• LMOD1
• Lauren classification
• Peritoneal metastasis
• WGCNA

Survival times differ among patients with advanced gastric carcinoma. A precise and universal prognostic evaluation strategy has not yet been established. The current study aimed to construct a prognostic scoring model for mortality risk stratification in patients with advanced gastric carcinoma.

Patients with advanced gastric carcinoma from two hospitals (development and validation cohort) were included. Cox proportional hazards regression analysis was conducted to identify independent risk factors for survival. A prognostic nomogram model was developed using R statistics and validated both in bootstrap and external cohort. The concordance index and calibration curves were plotted to determine the discrimination and calibration of the model, respectively. The nomogram score and a simplified scoring system were developed to stratify patients in the two cohorts.

Development and validation cohort was comprised of 401 and 214 gastric cancer patients, respectively. Mucinous or non-mucinous histology, ECOG score, bone metastasis, ascites, hemoglobin concentration, serum albumin level, lactate dehydrogenase level, carcinoembryonic antigen level, and chemotherapy were finally incorporated into prognostic nomogram. The concordance indices were 0.689 (95% CI: 0.664 ~ 0.714) and 0.673 (95% CI: 0.632 ~ 0.714) for bootstrap and external validation. 100 and 200 were set as the cut-off values of nomogram score, patients in development cohort were stratified into low-, intermediate- and high-risk groups with median overall survival time 15.8 (95% CI: 12.2 ~ 19.5), 8.4 (95% CI: 6.7 ~ 10.2), and 3.9 (95% CI: 2.7 ~ 5.2) months, respectively; the cut-off values also worked well in validation cohort with different survival time in subgroups. A simplified model was also established and showed good consistency with the nomogram scoring model in both of development and validation cohorts.

The prognostic scoring model and its simplified surrogate can be used as tools for mortality risk stratification in patients with advanced gastric carcinoma.

The online version contains supplementary material available at 10.1186/s12885-021-09079-7.

• Neoplasm metastasis
• Nomograms
• Stomach neoplasms
• Survival analysis

Gastric cancer (GC) is one of the most malignant diseases and threatens the health of individuals across the globe. Hitherto, the identification of prognosis risk stratification on GC has mainly depended on the TNM staging, but owing to its inaccuracy and incompleteness, the prognostic value it offers remains controversial in the current clinical setting. Thus, an effective prognostic model for GC after radical gastrectomy is still needed.

Patients with pathologically confirmed GC who underwent radical gastrectomy from 2 different centers were retrospectively enrolled into a training and the validation cohort, respectively. The least absolute shrinkage and selection operator (LASSO) algorithm was applied to select variables among multiple factors, including clinical characteristics, pathological parameters, and surgery- and treatment-related indicators. The multivariate Cox regression method was used to establish the model to predict 1-, 2-, and 3-year survival. Both internal and external validations of the nomogram were then completed in terms of discrimination, calibration, and clinical utility. Finally, prognostic risk stratification of GC was conducted with X-tile software.

A total of 1,424 patients with GC were eligible in this study, including 1,010 in the training cohort and 414 in the validation cohort. Seven indicators were selected by LASSO to develop the nomogram, including the number of positive lymph nodes, tumor size, adjacent organ invasion, vascular invasion, the level of carbohydrate antigen 125 (CA 125), depth of invasion, and human epidermal growth factor receptor 2 (HER2) status. The nomogram demonstrated a robust predictive capacity with favorable accuracy, discrimination, and clinical utility both in the internal and external validations. Moreover, we divided the population into 3 risk groups of survival according to the cutoff points generated by X-tile, and in this way, the nomogram was further improved into a risk-stratified prognosis model.

We have developed a prognostic risk stratification nomogram for GC patients after radical gastrectomy with 7 available indicators that may guide clinical practice and help facilitate tailored decision-making, thus avoiding overtreatment or undertreatment and improving communication between clinicians and patients.

• Gastric cancer (GC)
• external validation
• human epidermal growth factor receptor 2 (HER2)
• nomogram
• prognosis

• HER2
• gastric cancer
• pyrotinib
• trastuzumab

We conducted a single-arm phase II trial to investigate the short-term efficacy and safety of apatinib combined with oxaliplatin and S-1 in the treatment of unresectable gastric cancer.

Previously untreated patients with unresectable HER-2-negative advanced gastric cancer were selected. All the patients received six cycles of S-1 and oxaliplatin and five cycles of apatinib, which were administered at intervals of three weeks. The surgery was performed after six cycles of drug treatment. The primary endpoints were radical resection (R0) rate and safety. This study was registered with the China Trial Register, number ChiCTR-ONC-17010430 (01/12/2016–01/12/2022).

A total of 39 patients were enrolled. Efficacy evaluation was feasible for 37 patients. One patient achieved complete response (CR, 2.7%), 26 patients achieved partial response (PR, 70.3%), three patients had stable disease (SD, 8.1%) and seven patients had progressive disease (PD, 18.9%). The objective response rate (ORR) was 73.0% and the disease control rate (DCR) was 81.1%. 22 patients underwent surgery, among which 14 patients underwent radical resection (R0), with a R0 resection rate of 63.6%. The 1-year survival rate of the surgical group (22 patients) was 71.1% and the 2-year survival rate was 41.1%. The median survival time was 21 months. The incidence of adverse events (AEs) was 100%. Leucopenia (65.3%) and granulocytopenia (69.2%) were the most common hematological AEs. The most common non-hematological AEs were fatigue (51.3%) and oral mucositis (35.9%).

Apatinib combined with oxaliplatin and S-1 showed good short-term survival and acceptable safety in the conversion therapy of unresectable gastric cancer.

• Apatinib
• Conversion therapy
• Efficacy
• Safety
• Unresectable gastric cancer

An increasing number of reports have found that immune-related genes (IRGs) have a significant impact on the prognosis of a variety of cancers, but the prognostic value of IRGs in gastric cancer (GC) has not been fully elucidated.

Univariate Cox regression analysis was adopted for the identification of prognostic IRGs in three independent cohorts (GSE62254, n = 300; GSE15459, n = 191; and GSE26901, n = 109). After obtaining the intersecting prognostic genes, the three independent cohorts were merged into a training cohort (n = 600) to establish a prognostic model. The risk score was determined using multivariate Cox and LASSO regression analyses. Patients were classified into low-risk and high-risk groups according to the median risk score. The risk score performance was validated externally in the three independent cohorts (GSE26253, n = 432; GSE84437, n = 431; and TCGA, n = 336). Immune cell infiltration (ICI) was quantified by the CIBERSORT method.

A risk score comprising nine genes showed high accuracy for the prediction of the overall survival (OS) of patients with GC in the training cohort (AUC > 0.7). The risk of death was found to have a positive correlation with the risk score. The univariate and multivariate Cox regression analyses revealed that the risk score was an independent indicator of the prognosis of patients with GC (p < 0.001). External validation confirmed the universal applicability of the risk score. The low-risk group presented a lower infiltration level of M2 macrophages than the high-risk group (p < 0.001), and the prognosis of patients with GC with a higher infiltration level of M2 macrophages was poor (p = 0.011). According to clinical correlation analysis, compared with patients with the diffuse and mixed type of GC, those with the Lauren classification intestinal GC type had a significantly lower risk score (p = 0.00085). The patients' risk score increased with the progression of the clinicopathological stage.

In this study, we constructed and validated a robust prognostic signature for GC, which may help improve the prognostic assessment system and treatment strategy for GC.

• Gastric cancer (GC)
• biomarker
• human epidermal growth factor receptor 2 amplification
• microsatellite instability (MSI)
• tumor mutational burden (TMB)

• gastric cancer
• diffuse‑type
• bioinformatics
• differentially expressed gene

Although circulating cell-free DNA (cfDNA) is a promising biomarker for the diagnosis and prognosis of various tumors, clinical correlation of cfDNA with gastric cancer has not been fully understood. To address this, we developed a highly sensitive cfDNA capture system by integrating polydopamine (PDA) and silica. PDA-silica hybrids incorporated different molecular interactions to a single system, enhancing cfDNA capture by 1.34-fold compared to the conventional silica-based approach (p = 0.001), which was confirmed using cell culture supernatants. A clinical study using human plasma samples revealed that the diagnostic accuracy of the new system to be superior than the commercially available cfDNA kit, as well as other serum antigen tests. Among the cancer patients, plasma cfDNA levels exhibited a good correlation with the size of a tumor. cfDNA was also predicative of distant metastasis, as the median cfDNA levels of metastatic cancer patients were ~60-fold higher than those without metastasis (p = 0.008). Furthermore, high concordance between tissue biopsy and cfDNA genomic analysis was found, as HER2 expression in cfDNA demonstrated an area under ROC curve (AUC) of 0.976 (p <0.001) for detecting patients with HER2-positive tumors. The new system also revealed high prognostic capability of cfDNA, as the concentration of cfDNA was highly associated with the survival outcomes. Our novel technology demonstrates the potential to achieve efficient detection of cfDNA that may serve as a reliable biomarker for gastric tumor.

• Adult
• Aged
• Aged, 80 and over
• Biomarkers, Tumor/blood
• Biomarkers, Tumor/genetics
• Cell-Free Nucleic Acids/genetics
• Cell-Free Nucleic Acids/isolation & purification
• Early Detection of Cancer
• Female
• Humans
• Male
• Middle Aged
• Prognosis
• Silicon Dioxide/chemistry
• Stomach Neoplasms/blood
• Stomach Neoplasms/diagnosis
• Stomach Neoplasms/genetics
• Stomach Neoplasms/pathology

• P50 DE026787 NIDCR NIH HHS
• Wisconsin Head & Neck Cancer SPORE

• Autophagy
• Gastric adenocarcinoma
• Gastric cancer
• Non coding RNAs
• Novel targets
• Piwi RNA
• lncRNA

• Animals
• Biomarkers, Tumor/metabolism
• Clinical Trials, Phase II as Topic
• Clinical Trials, Phase III as Topic
• Combined Modality Therapy
• Epstein-Barr Virus Infections/pathology
• Helicobacter Infections/pathology
• Helicobacter pylori/isolation & purification
• Herpesvirus 4, Human/isolation & purification
• Humans
• Molecular Targeted Therapy
• Neoplasm Staging
• Randomized Controlled Trials as Topic
• Stomach Neoplasms/metabolism
• Stomach Neoplasms/microbiology
• Stomach Neoplasms/pathology
• Stomach Neoplasms/therapy

• R37 CA215427 NCI NIH HHS

• FISH
• HER2 overexpression
• Microvessel density
• Tumor angiogenesis

This study was to investigate the prognostic factors of patients with advanced gastric cancer and described a sample model to better differentiate the patients who could better benefit from palliative chemotherapy.

In this retrospective study, 112 gastric cancer patients at stage IV following first-line chemotherapy were enrolled from July 2013 to September 2019. The clinical factors including age, sex, ECOG, pathologic types, metastatic sites, blood indexes, response of first-line chemotherapy, and survival were collected. The treatment responses were evaluated using the response evaluation criteria in solid tumors (RECIST). The survival curves were drawn by the Kaplan–Meier method, and the independent prognostic factors of overall survival (OS) were analyzed by Cox proportional hazards regression model.

In this study, the median overall survival (mOS) of gastric cancer patients was 10.5 months, the disease remission rate (PR) was 21.4%, and the disease control rate (DCR) was 86.6%. Multivariate analysis identified 5 independent prognostic factors: peritoneal metastasis [P = 0.002; hazard risk (HR), 2.394; 95% CI 1.394–4.113], hemoglobin <90g/L [P = 0.001; hazard risk (HR), 2.674; 95% CI 1.536–4.655], LDH ≥225 U/L [P = 0.033; hazard risk (HR), 1.818; 95% CI 1.409–3.150], and 3 times higher level of CEA [P = 0.006; hazard risk (HR), 2.123; 95% CI 1.238–3.640] along with CA199 [P = 0.005; hazard risk (HR), 2.544; 95% CI 1.332–4.856] than upper limit of normal. Based on the obtained data, a prognostic index was constructed, dividing the patients into three risk groups: low (n = 67), intermediate (n = 35), and high-risk group (n = 10). The mOS for low, intermediate, and high-risk groups was 13.9 months (95% CI 10.7–17.1), 8.1 months (95% CI 5.7–10.4), and 3.9 months (95% CI 2.6–5.3), respectively, whereas the 1-year survival rate was 56.4%, 20.0%, and 0.0%, respectively (P < 0.001).

This model should facilitate the prediction of treatment outcomes and then individualized treatment of advanced gastric cancer patients.

• advanced gastric cancer
• first-line chemotherapy
• prognosis model
• prognostic factor

A randomized clinical trial showed that trastuzumab, added to traditional chemotherapy, significantly improved overall survival in human epidermal growth factor receptor 2 (HER2)-overexpressing metastatic gastric cancer patients. This population-based study aimed at evaluating both the clinical and economic impact of trastuzumab in a real-world setting. By using the healthcare utilization databases of Lombardy, Italy, a cohort of patients newly diagnosed with metastatic gastric cancer during the period 2011–2016 was selected. Among these, patients initially treated with either trastuzumab-based chemotherapy or standard chemotherapy alone were followed up until death, migration in other regions or June 2018. Overall survival and average cumulative costs were estimated and compared between the two treatment arms. Among the 1198 metastatic gastric cancer patients who started therapy within six months after metastasis detection, 87 were initially treated with trastuzumab-based chemotherapy and 1111 with standard chemotherapy. Median overall survival and restricted mean survival were 10.2 and 7.4 months, and 14.9 and 11.4 months, respectively, in the two treatment arms. The adjusted hazard ratio of death was 0.73 (95% CI 0.57–0.93). The average per capita cumulative healthcare costs were, respectively, EUR 39,337 and 26,504, corresponding to an incremental cost-effectiveness ratio of EUR 43,998 for each year of survival gained. Our study shows that adding trastuzumab to conventional chemotherapy is effective and cost-effective.

• cost-effectiveness
• gastric cancer
• overall survival
• real-word evidence
• trastuzumab

• Gastric cancer
• HER2
• Immunohistochemistry

• KRAS
• digestive tract malignant tumor
• esophageal squamous carcinoma
• gastric carcinoma and colorectal cancer
• guanine nucleotide exchange factor T
• human epidermal growth factor receptor-2
• microsatellite instability

Gastric cancer (GC) is one of the most common malignant tumors in the world. As anti-angiogenic therapy shows efficacy in the treatment of GC, but only works in certain patients, the identification of potential beneficiaries are urgently required in order to apply appropriate treatments. The Lauren classification demonstrates numerous differences in etiology, epidemiology and pathology; however, the association between Lauren classification and pro-angiogenic factors remains unclear. The present study aimed to investigate the clinicopathological factors associated with Lauren classification and the prognostic significance of Lauren classification and vascular endothelial growth factor (VEGF) and VEGF receptor-2 (VEGFR-2) expression in GC. Paraffin-embedded GC tissues and clinical information of 255 patients with GC were collected. The clinicopathological factors associated with Lauren classification were evaluated by Logistic regression analysis. Kaplan-Meier survival and Cox regression analyses were used to examine the prognostic significance of Lauren classification and of VEGF and VEGFR-2 expression in patients with GC. The results demonstrated that there was no association between Lauren classification and VEGF and VEGFR-2 expression. Furthermore, results from survival analysis demonstrated that Lauren classification (P=0.001) and Tumor-Node-Metastasis stage (stage II, P=0.002; stage III, P<0.001) were independent prognostic factors in GC. Following subgroup analysis based on Tumor-Node-Metastasis stage, Lauren classification was demonstrated to be an independent prognostic factor in patients with stage III GC (P=0.010) but not in patients with stage I or II GC. Furthermore, VEGFR-2 overexpression was an independent predictor of survival in intestinal-type GC (P=0.040) but not in diffuse-type GC. Taken together, these results indicate that Lauren classification may serve as an independent prognostic factor for patients with GC. In addition, although the expression of VEGF and VEGFR-2 was not associated with Lauren classification, VEGFR-2 overexpression may be considered as an independent prognostic factor in intestinal-type GC.

• Lauren classification
• gastric cancer
• prognosis
• vascular endothelial growth factor
• vascular endothelial growth factor receptor-2

• Chemotherapy
• China
• Gastric cancer
• Gastroesophageal junction cancer
• HER2
• Overall survival
• Pertuzumab
• Progression-free survival
• Safety
• Trastuzumab

• chemotherapy
• gastric cancer
• pathological complete response
• trans-arterial chemotherapy and embolization

• Administration, Oral
• Chemoembolization, Therapeutic/methods
• China
• Drug Therapy/methods
• Gastrectomy/methods
• Humans
• Laparoscopy/methods
• Lymph Node Excision/methods
• Male
• Middle Aged
• Prognosis
• Stomach Neoplasms/drug therapy
• Stomach Neoplasms/surgery
• Tomography, X-Ray Computed/methods

• Adjuvant
• Chemotherapy
• Chinese Society of Clinical Oncology (CSCO)
• Diagnosis
• Gastric cancer
• Immunotherapy
• Neoadjuvant
• Radiotherapy
• Surgery
• Targeted therapy

• China
• Humans
• Medical Oncology
• Societies, Medical
• Stomach Neoplasms/diagnosis
• Stomach Neoplasms/therapy

• AB007962
• The Cancer Genome Atlas
• intestinal-type gastric cancer
• long non-coding RNA
• prognosis
• reverse transcription-quantitative polymerase chain reaction

• Gastric cancer
• HER2
• HIF-1α
• LDHA
• migration

The hematogenous metastatic pattern of gastric cancer (GC) was not fully explored. Here we analyzed the frequency and clinicopathological features of metastasis to liver, lung, bone, and brain from GC patients. Data queried for this analysis included GC patients from the Surveillance, Epidemiology, and End Results Program database from 2010 to 2014. All of statistical analyses were performed using the Intercooled Stata 13.0 (Stata Corporation, College Station, TX). All statistical tests were two‐sided. Totally, there were 19 022 eligible patients for analysis. At the time of diagnosis, there were 7792 patients at stage IV, including 3218 (41.30%) patients with liver metastasis, 1126 (14.45%) with lung metastasis, 966 (12.40%) with bone metastasis and 151 (1.94%) with brain metastasis. GC patients with lung or liver metastasis have a higher risk of bone and brain metastasis than those without lung nor liver metastasis. Intestinal subtype had significantly higher rate of liver and lung metastasis, while diffuse type was more likely to have bone metastasis. Proximal stomach had significantly higher risk to develop metastasis than distal stomach. African‐Americans had the highest risk of liver metastasis and Caucasian had the highest prone to develop lung and brain metastasis. The median survival for patients with liver, lung, bone, and brain metastasis was 4 months, 3 months, 4 months and 3 months, respectively. It is important to evaluate the status of bone and brain metastasis in GC patients with lung or liver metastasis. Knowledge of metastatic patterns is helpful for clinicians to design personalized pretreatment imaging evaluation for GC patients.

• SEER
• gastric cancer
• metastases

Factors affecting trastuzumab efficacy in advanced gastric cancer (GC) are largely unknown. Heterogeneity is a notable feature of HER2 in GC. Whether the heterogeneity influences trastuzumab efficacy is still unknown.

The HER2^homogeneous group and HER2^{heterogeneous} group showed no statistical difference in RR (46.4% vs 55.0%, P = 0.558), PFS (5.80 vs 6.30 months, P = 0.804) and OS (16.00 vs 16.00 months, P = 0.787). The Lauren^intestinal group and Lauren^{non-intestinal} group demonstrated no discrepancy in PFS (6.00 vs 6.00 months, P = 0.912) and OS (16.50 vs 14.00 months, P = 0.227). However, by combining HER2 heterogeneity and Lauren classification, PFS and OS of HER2^homogeneous/Lauren^{non-intestinal} subgroup was the shortest among the 4 subgroups (P = 0.012 and P = 0.037), which was much shorter than the other patients (PFS:3.00 vs 6.30 months, P = 0.003; OS: 4.50 vs 16.50 months, P = 0.004). Univariate and multivariate analysis showed that HER2 heterogeneity combined with Lauren classification was an independent prognostic factor in both PFS (P = 0.031 and P = 0.002) and OS (P = 0.039 and P = 0.013).

48 patients with HER2 positive advanced GCs accepting trastuzumab treatment were retrospectively analyzed. Based on HER2 heterogeneity, the patients were divided into a HER2^homogeneous group and a HER2^{heterogeneous} group. Response rate (RR), progression free survival (PFS), and overall survival (OS) were compared. Main clinicopathological factors including Lauren classification were subjected to subgroup analysis.

HER2 heterogeneity alone may not correlate with trastuzumab efficacy in HER2 positive advanced GCs. HER2 heterogeneity combined with Lauren classification may help to identify a subgroup with poor response to trastuzumab which is homogeneous HER2 positive and non-intestinal type.

• HER2
• efficacy
• gastric cancer
• heterogeneity
• trastuzumab

The prognostic implications of human epidermal growth receptor 2 (HER2) heterogeneity in gastric cancer (GC) are not well established. Therefore, the aim of the present study was to determine to the effect of HER2 status on the prognosis of GC patients. We retrieved data on 248 pathologically-confirmed, consecutive patients with primary adenocarcinoma of the stomach or gastro-esophageal junction who underwent surgical resection at Kurume University Medical Center between July 2000 and December 2012. HER2 status was classified as HER2 positive or negative and HER2 heterogeneity or homogeneity. The endpoint was overall survival (OS), which was compared using the generalized Wilcoxon test. HER2 status was positive in 36 patients (14.5%) and negative in 212 patients (85.5%). Among the 36 HER2 positive patients, 25 patients (69.4%) had HER2 heterogeneity and the remaining 11 patients (30.6%) had HER2 homogeneity. Among the 141 patients with stage III or IV disease, the prognosis of the HER2 homogeneity group was significantly worse than that of the HER2 heterogeneity group (p = 0.019; median OS 193 and 831 days, respectively). The prognosis was not significantly different between the HER2 positive group and the HER2 negative group (p = 0.84; median OS 552 and 556 days, respectively). The present study was conducted with small samples, however, the results of the study suggest that HER2 homogeneity but not HER2 positivity may represent a prognostic indicator in GC.

• HER2
• gastric cancer
• intratumoral heterogeneity
• prognosis
• trastuzumab

The single nucleotide polymorphism (SNP) rs2910164 G>C within miR-146a has been reported that is associated with the increased risk of gastric cancer (GCa). However, the results are inconclusive, espicially among Asian populations, which probably due to small sample size in each single study. To validate this association and get a more precise estimation, we conducted a large GCa study including 1,125 cases and 1,196 controls in an eastern Chinese population. Our results showed that this SNP was not associated with GCa risk in either of the three genetic models [co-dominant model: CG vs. CC, odds ratio (OR) = 0.99, 95% confidence interval (95%CI): 0.83-1.19; GG vs. CC, OR = 1.03, 95%CI: 0.81-1.32; dominant model: (CG+GG) vs. CC, OR = 1.00, 95%CI = 0.84-1.19; recessive model: GG vs. (CG+CC), OR = 1.04, 95%CI = 0.83-1.29]. Stratified analysis by age, gender, smoking status, drinking status, or tumor location confirmed this non-significant association. In summary, these results suggest that the miR-146a SNP rs2910164 may not be a risk factor for GCa in this Chinese population. Larger and well-designed, preferably prospective studies are needed to further confirm our findings.

• gastric cancer
• genetic susceptibility
• miR-146a
• polymorphism

• her2
• meta-analysis
• prognostic
• stomach neoplasm

• Aged
• Antineoplastic Agents/therapeutic use
• Female
• Humans
• Male
• Middle Aged
• Patient Selection
• Prognosis
• Receptor, ErbB-2/analysis
• Stomach Neoplasms/chemistry
• Stomach Neoplasms/drug therapy
• Stomach Neoplasms/pathology
• Trastuzumab/therapeutic use
• Treatment Outcome

Purpose: Patients with advanced or metastatic adenocarcinoma of the stomach or esophagogastric junction for whom trastuzumab therapy is being considered, assessment for tumor human epidermal growth factor receptor-2 (HER2) status is necessary. Can the HER2 status and Lauren classification of the biopsy sample truly represent the HER2 status in the gastric cancer?

Methods: Formalin-fixed, paraffin-embedded sections of 116 pair surgically resected and biopsy specimens as well as 80 pair primary and metastatic lesions of gastric cancer patients were analyzed. Protein expression was assessed using immunohistochemistry (IHC) and graded by the modified scoring criteria for gastric cancer. Gene amplification was evaluated by fluorescence in situ hybridization (FISH) in IHC 2+ cases.

Results: The positive rate of HER2 was 11.2% in both surgical and biopsy samples. The consistent rate of HER2 expression was 91.4% (106/116) between biopsy and surgical samples, P=0.666. The positive rate of HER2 was 20.5% in primary and 15.9% in metastatic samples, P=0.1876. The consistent rate of HER2 expression was 90.9% (40/44) between primary and metastatic samples, P=0.580. The consistent rate of Lauren classification was 64.7% (75/116) between biopsy and surgical sample, and 92.5% (74/80) between primary and metastatic samples.

Discussion: For gastric cancer, HER2 expression and Lauren classification were highly homogenous in biopsy and surgical samples, primary and their corresponding metastatic samples. The high concordance observed between these two cohorts indicated that the HER2 examination and Lauren classification of biopsy samples from the primary tumor could well represent the metastatic lesions of the patients.

• FISH.
• Gastric Cancer
• HER2
• Immunohistochemistry

Human epidermal growth factor receptor 2 (HER2) is involved in the pathogenesis of several types of cancer, including gastric cancer. Overexpression of HER2 is noted in 10%–22.8% of gastric adenocarcinoma and its identification is of immense importance for management by targeted drugs. Detection of HER2 expression in gastric malignancies has not been undertaken previously in the local population.

To ascertain HER2 immunohistochemical expression in gastric adenocarcinoma and its relationship with the anatomic location and histomorphology.

A total of 47 cases of gastric adenocarcinoma diagnosed over 2 years constituted the study group. Clinical history, type of operation, gross morphology, and hematoxylin and eosin (H and E) stained sections were reviewed. Two paraffin blocks were selected, immunostain was performed using rabbit monoclonal HER2 antibody and Hoffmann scoring system was applied.

Most of gastric carcinomas occurred in male (42 cases), having a mean age of 53.6 years. A total of eight cases (17.1%) had expressed a score of 3+ HER2 positivity. All positivity was noted in intestinal type according to Lauren classification (25%) and none in diffuse type. All HER2 score of 3+ was noted in histological grade of well and moderately differentiated adenocarcinoma. Score 2+ was noted in seven cases, among them, only two were poorly differentiated gastric adenocarcinoma.

HER2 overexpression was noticeably associated with an intestinal subtype, and well and moderately differentiated adenocarcinomas. Such cases of gastric adenocarcinoma are considered for targeted therapy with trastuzumab in the local population.

• Gastric adenocarcinoma
• histological grade
• human epidermal growth factor receptor 2 expression
• human epidermal growth factor receptor 2 score

• Adverse prognosis
• Gastric carcinoma
• HER2 expression
• Survival

Human epidermal growth factor receptor-2 (HER2) is regarded as an important and promising target in the treatment of HER2-positive breast cancers. However, the correlation of clinicopathological characteristics and prognostic significance of HER2 overexpression in gastric cancer patients remains unclear. Our aim was to clarify this issue.

Embase, PubMed, and the Cochrane Library were searched for relevant articles published up to May 2016. Outcomes of interest contained sex, age, tumor size, tumor site, tumor node metastasis (TNM) stage, distant metastasis, lymph node metastasis, Lauren’s classification, differentiation grade, lymphovascular invasion, neural invasion, and multivariate analysis data for overall survival.

A total of 41 studies of 17,494 gastric cancer patients were identified with HER2 test. HER2 positive rate was 19.07% (95% CI = 9.16, 28.98). There existed statistical significance between HER2 overexpression and patients’ prognosis (RR = 1.47, 95% CI = 1.09, 1.98). Male patients (OR = 1.48, 95% CI = 1.34, 1.65), proximal tumors (OR = 1.25, 95% CI = 1.07, 1.47), intestinal-type tumors (OR = 3.37, 95% CI = 2.54, 4.47), advanced stage cancers (OR = 1.35, 95% CI = 1.10, 1.66), lymph node metastasis (OR = 1.26, 95% CI = 1.14, 1.41), well-differentiated cancers (OR = 1.79, 95% CI = 1.15, 2.76), and distant metastasis (OR = 1.91, 95% CI = 1.08, 3.38) were correlated with higher HER2 expression rates. However, no statistical differences existed in age, tumor size, lymphovascular invasion, or neural invasion. Subgroup analysis revealed that HER2 expression rates reported in articles from Asian (19.52%) countries were quantitatively higher than those from European (16.91%) areas. Results were consistent with those reports that define HER2 status according to trastuzumab for gastric cancer (ToGA) criteria.

This study showed that HER2 overexpression was associated with poor prognosis in gastric cancer patients. HER2 positive rates may be associated with sex, tumor site, TNM staging system, distant metastasis, lymph node metastasis, Lauren’s classification, and differentiation grade in gastric cancer patients. The HER2 expression rate in Asians may be higher than that in Europeans. This study offers a convenient way for doctors to select patients for relevant HER2 detection and following treatment.

The online version of this article (doi:10.1186/s12957-017-1132-5) contains supplementary material, which is available to authorized users.

• Gastric cancer
• HER2/neu
• Meta
• Prognosis