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

• Published in: BJC Reports 2024-08, Vol.2 (1), p.58-8
• Main Authors: Biesma, H D, Soeratram, T T D, van Essen, H F, Egthuijsen, J M P, Poell, J B, van Dijk, E, Meershoek-Klein Kranenbarg, E, Hartgrink, H H, van de Velde, C J H, van de Wiel, M A, Ylstra, B, van Grieken, N C T
• Format: Article
• Language: English
• ISSN: 2731-9377; 2731-9377
• DOI: 10.1038/s44276-024-00078-2

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. 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). 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. 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.