Clinicopathologic and genomic characteristics of mucinous gastric adenocarcinoma.

Abstract

Mucinous gastric adenocarcinoma (MGC) is a rare but distinctive histologic subtype of gastric cancer (GC). The clinico-pathologic and genomic characteristics of MGC have not been well evaluated. We collected individual data from five cohorts targeting the microsatellite instability (MSI) of GC (n = 5089) to evaluate the clinico-pathologic characteristics of MGC. In addition, public genomic databases were used for genomic analysis. The characteristics of MGC were compared with those of non-mucinous GC (NMGC). MGC (n = 158, 3.1%) showed distinctive characteristics in terms of age, sex, and TNM stage compared to NMGC (n = 4931). MGC was frequently associated with MSI-high (OR: 2.24, 95% confidence interval [CI] 1.44-3.40, p < 0.001), while mutually exclusive to the Epstein-Barr virus type. The prognosis of MGC was better than that of NMGC (adj.HR: 0.731, 95% CI 0.556-0.962, p = 0.025). There was no clear benefit from postoperative chemotherapy in MGC. TP53 was the main driver mutation in the MGC without recurrent variants. MGC was related to high expression of GPR120 and B3GNT6 and moderate regulation of epithelial-mesenchymal transition (EMT)-up signature with a high EMT-down signature, and those characteristics was related to favorable prognosis of GC (log-rank p = 0.044, p < 0.001, p < 0.001, respectively). MSI-H of MGC was associated with low cancer-associate fibroblasts but high CD274 (PD-L1) expression compared to microsatellite stable MGC, suggesting that immune checkpoint inhibitors may be useful for the MSI-H of MGC. MGC could be a surrogate for performing MSI but not the EBV test in GC. Further, its genetic characteristics lead to a favorable prognosis for MGC.