[Another sight at Gastric Cancer Molecular Classification: novel subtypes based on expression of CDX-2, E-cadherin,...

This study explores the immunohistochemical and prognostic characteristics of gastric cancer (GC).

The research analyzed surgical samples from 310 GC patients who had not received chemotherapy or radiotherapy prior to surgery. Each sample was immunohistochemically stained for 23 markers (MSH2, MSH6, MLH1, PMS2, MUC2, CDX2, MUC5AC, CD10, E-cadherin, β-catenin, Claudin-1, Claudin-3, Claudin-4, CD44, p53, PD-L1 (SP142), PD-L1 (SP236), HER2, CD4, CD8, CD68, CD1a, LMP-1), and in situ hybridization for Epstein-Barr virus RNA (EBER) was also conducted.

The analysis led to the development of a molecular classification of gastric cancer, comprising five molecular subtypes: MMR-deficient, EBER-positive, E-cadherin aberrant, CDX2-positive, and CDX2-negative. The CDX2-positive subtype occurs in 49.7% of GC cases; it includes papillary and mucinous GC with less depth of invasion, no lymph node involvement, and lower clinical stage and has a relatively favorable prognosis (median survival 47 months). The CDX2-negative subtype occurs in 16.1% of GC cases; it includes tumors of diffuse and intermediate type by P. Lauren, primarily located distally in the stomach, with a greater depth of invasion and a higher clinical stage. The CDX2-negative subtype is characterized by positive expression of MUC5AC and unfavorable prognosis (median survival 23 months).

A new five-tier molecular classification of gastric cancer has been developed. Two of the five subtypes have been identified and characterized for the first time. The identified subtypes have promising implications for the targeted therapy of gastric malignancies.