Distinct expression profile of key molecules in crawling-type early gastric carcinoma

Background: Gastric “crawling-type” adenocarcinoma (CRA) is a tumor histologically characterized by irregularly fused glands with low-grade cellular atypia that tends to spread laterally in the mucosa. To date, the expression characteristics of the key molecules involved in CRA, including receptor tyrosine kinases (RTKs), mismatch repair (MMR) proteins, phosphatase and tensin homolog (PTEN), as well as the Epstein–Barr virus (EBV) status, have yet to be uncovered. Methods: We constructed tissue microarrays of 94 CRAs, 72 conventional-type differentiated adenocarcinomas (CDAs), and 71 intramucosal poorly cohesive adenocarcinomas (PCAs) from early gastric cancers to evaluate and compare the pathological and expression profiles of potential key molecules for molecular classification (EBV; four MMR proteins–MLH1, MSH2, PMS2, and MSH6; three RTKs–HER2, MET, and EGFR; PTEN; and p53). Results: None of the CRAs showed MMR deficiency (0.0 % vs. 5.6 %, CRA vs. CDA, p = 0.036), HER2 overexpression (0.0 % vs. 12.5 %, p = 0.001), or loss of PTEN expression (0.0 % vs. 9.7 %, p = 0.003). Moreover, MET overexpression (4.4 % vs. 19.4 %, p = 0.004), and a mutant p53 pattern (12.4 % vs. 62.5 %, p < 0.001) were significantly less common in CRAs than in CDAs. However, clinicopathological features and all the profile of the molecules of CRAs were close to those of the PCA group. Conclusions: CRA demonstrated unique clinicopathological characteristics and showed a distinct expression profile of key molecules, which was close to that of a null phenotype. These results support the classification of CRA as a distinct subgroup of gastric adenocarcinoma.