Further prognostic stratification of intestinal type of gastric adenocarcinoma by CDX2 expression pattern

Gastric cancer is one of the most deadly malignancies worldwide. It is routinely divided into 2 common histologic subtypes by the Lauren classification, intestinal type and diffuse type. In recent years, the intestinal type of gastric cancer has been found to represent a heterogeneous disease with divergent prognosis. Our objective was to investigate the CDX2/CK7 immunohistochemical pattern and its role in further stratifying this type of gastric cancer. Gastrectomy cases with a diagnosis of the intestinal type of gastric adenocarcinoma from a single large institution between 2008 and 2022 were collected. Forty-four cases with available blocks and enough tumor tissue were included in this study. Four different immunohistochemical patterns were identified: CDX2+/CK7+ (40.9%), CDX2-/CK7+ (34.1%), CDX2+/CK7- (18.2%), and CDX2-/CK7- (6.8%). Compared to CDX2-negative cases, CDX2-positive ones are more likely to present better prognostic histopathological features including early stage, less perineural and lymphovascular invasion, and lower nodal metastasis. In addition, CDX2 expression was associated with specific molecular features like HER2 overexpression and genetic alterations of receptor tyrosine kinase (TRK) genes including EGFR, ERBB2, ERBB3, DDR2, and MET. In conclusion, according to the CDX2 expression pattern, the intestinal type of gastric cancer could be further divided into 2 subgroups, which have different histopathological and molecular features and different prognosis.