Immunohistochemical classification of gastric cancer based on new molecular biomarkers: a potential predictor of survival

Abstract

Several classification systems have been described for stratifying patients with gastric carcinoma (GC). However, their prognostic value is low, and there is an urgent need for identification of molecular markers and development of new classifications. Retrospective study of 206 cases of GC diagnosed and surgically resected in our hospital between 2000 and 2017. Clinicopathological features of all cases were assessed and tissue microarrays were constructed for immunohistochemical (IHC) study. Patients were stratified based on IHC results. Mean patient age was 71 years and most patients were male (54.6%). Most tumors were located in the gastric antrum and body, and they were mostly fungoid or ulcerative lesions. GC were mainly intestinal-type tumors and 60.3% were diagnosed at pT3. 56.2% of patients showed recurrences and 29.4% died due to GC. According to our IHC classification, 23.5% of tumors showed microsatellite instability, 6% were E-cadherin negative, 53.5% were stable-p53 not overexpressed, and 17% were stable with p53 overexpression. IHC classification was significantly correlated with patient gender, gross morphology, Laurén classification, tumor necrosis, perineural infiltration, type of leading edge, and patient outcome. Multivariate analysis showed that IHC subtype was significantly and independently associated with overall survival, together with clinical symptoms, signet cell phenotype, tumor grade and vessel invasion. The application of IHC classifications based on molecular biomarkers in clinical practice can aid in the stratification of GC patients. More studies are needed to evaluate the reproducibility and clinical significance of these classifications.

Preservation of Epstein–Barr virus status and mismatch repair protein status along the metastatic course of gastric cancer

“…We therefore analysed EBV and MMR protein status in the primary tumours and corresponding metastases in a large western cohort of resected primary GC. The frequency of EBV‐positive and MMR‐deficient tumours in our cohort is slightly lower compared to GC cohorts in previous publications, where EBV‐positive tumours occurred in a range of between 4 and 14% and MMR‐deficient tumours between 8 and 26% 5,7‐11,16 . We hypothesise that the observed differences of EBV frequency are due mainly to the different patient populations under study, and reflect the known geographical variation in EBV positivity, with both ethnicity and lifestyle as well as environmental risk factors and coinfections as contributing factors 17 .…”

“…These molecular subtypes can be detected using routine immunohistochemistry and in‐situ hybridisation techniques, as demonstrated by previous studies. In particular, identification of EBV‐positive and MSI tumours can be accomplished by using Epstein–Barr‐encoding region (EBER) in‐situ hybridisation and mismatch repair (MMR) protein (MLH1, PMS2, MSH2 and MSH6) immunohistochemistry 8‐10 . The concordance rate of MMR expression profiles by immunohistochemistry and microsatellite instability testing has been shown to be as high as 99% for GC 11 .…”

Clinical Stratification of High-Grade Ovarian Serous Carcinoma Using a Panel of Six Biomarkers

“…Immunohistochemical (IHC) has become a significant tool in clinical diagnostics and is frequently utilized to classify malignant cells [7]. In gastric cancer, a panel of six biomarkers was used in tumor stratification [8,9]. In a similar approach, cancers of the endometrium [10,11], lung [12], triple-negative breast [13], esophagogastric junction carcinomas [14] were stratified into discrete molecular classes using tumor-specific IHC-based biomarkers.…”

Clinical Implementation of Precision Medicine in Gastric Cancer

“…These subgroups exhibited different clinicopathologic features including prognosis that were in accordance with a previously reported molecular classification. In a European cohort, 4 GC types were defined based on microsatellite stability and E-cadherin and p53 expression that showed differences in the survival, recurrence rate, and other clinical characteristics such as macroscopic morphology and Lauren classification [28]. Another study divided GC into 4 subgroups corresponding to TCGA classification based on EBV, MSI status, and p53 expression that differed in terms of survival probability and human epidermal growth factor receptor 2 (HER2) positivity [29].…”