New substituted molecular classifications of advanced gastric adenocarcinoma: characteristics and probable treatment strategies

Gastric adenocarcinoma (GA) is a heterogeneous tumor, and the accurate classifications are important. Previous classifications are based on molecular analysis and neglect GA with the primitive enterocyte phenotype (GAPEP), a unique subtype with a poor prognosis and frequent liver metastases. New substituted molecular (SM) classifications based on immunohistochemistry (IHC) are needed. According to the IHC staining results, we divided 582 cases into six types: mismatch repair deficient (dMMR), Epstein-Barr virus associated (EBVa), the primitive enterocyte phenotype (PEP), the epithelial mesenchymal transition (EMT) phenotype, not other special/P53 mutated (NOS/P53m) and not other special/P53 wild-type (NOS/P53w). We analyzed the clinicopathological features, immune microenvironment (PD-L1, CD8) and expression of HER2 and VEGFR2 of those types. There were 31 (5.3%) cases of the dMMR type, 13 (2.2%) cases of the EBVa type, 44 (7.6%) cases of the PEP type, 122 (21.0%) cases of the EMT type, 127 (21.8%) cases of the NOS/P53m type and 245 (42.1%) cases of the NOS/P53w type. Patients with the dMMR type had the best survival (P