Chromosomal copy number based stratification of gastric cancer has added prognostic value to Lauren’s histological classification

Abstract

Abstract Background The Cancer Genome Atlas (TCGA) recognizes four molecular subgroups of gastric cancer: Epstein-Barr virus (EBV) positive, microsatellite instable (MSI), genomically stable (GS), and chromosomal instable (CIN). Since a GS/CIN classifier is lacking, alternative markers such as Lauren’s histopathology or CDH1/p53 immunohistochemistry are commonly applied. Here we compared survival of gastric cancer subgroups determined by four methods. Methods 309 EBV negative and microsatellite stable tumors were included from the Dutch D1/D2 trial and assigned to subgroups by: (i) TCGA’s specific chromosomal copy number aberrations, (ii) genome instability index (GII), (iii) Lauren’s classification, and (iv) CDH1/p53 immunohistochemistry. Subgroups were associated with cancer-related survival (CRS). Results Five-year CRS was 42.0% for diffuse and 49.5% for patients with intestinal type tumors, and 57.8% for GS and 41.6% for patients with CIN tumors. Classification by GII or CDH1/p53 IHC did not correlate with CRS. The combination of TCGA and Lauren classifications resulted in four distinct subgroups. Five-year CRS for GS-intestinal (n = 24), GS-diffuse (n = 57), CIN-intestinal (n = 142) and CIN-diffuse (n = 86) was 61.4%, 56.5%, 47.6%, and 31.5%, respectively. Conclusions TCGA’s GS and CIN subgroups have additional prognostic value to Lauren’s classification in resectable gastric cancer. GS-intestinal, GS-diffuse, CIN-intestinal and CIN-diffuse are suggested stratification variables for future studies.