Mucinous gastric carcinomas: clinicopathologic and molecular analyses

Background: Mucinous gastric carcinoma (MGC) is characterized by substantial mucous lakes within tumors and comprises 3% of gastric carcinomas at the authors' institute.

Methods: The authors analyzed the clinicopathologic characteristics, mucin gene expression profiles, microsatellite instability (MSI), and status of the human epidermal growth factor receptor 2 (HER-2) and epidermal growth factor receptor (EGFR) genes in 133 MGCs and compared them with the same variables in nonmucinous gastric carcinomas (NMGCs). In addition, the prognostic implications of clinicopathologic parameters were evaluated.

Results: Patients who had MGC had deeper invasion (P=.003), more frequent lymph node metastasis (P<.001), more advanced pathologic stage (P<.001), more frequent lymphatic invasion (P<.001), and lower disease-specific survival rates (P<.0001) than patients who had NMGC. However, a mucinous histology per se was not identified as an independent prognostic factor. Negative mucin 1, cell surface associated (MUC1) status (P<.001); positive mucin 2, oligomeric mucus/gel-forming (MUC2) status (P<.001); negative mucin 5AC, oligomeric mucus/gel-forming (MUC5AC) status (P=.036); and negative mucin 6, oligomeric mucus/gel-forming (MUC6) status (P<.001) were more frequent in MGCs. The frequency of MSI in MGC was not significantly different from that in NMGC. MGCs had a significantly lower incidence of HER-2 protein overexpression (P=.046), HER-2 gene amplification (P=.009), and EGFR protein overexpression (P=.017) than NMGCs; and multivariate analysis identified EGFR overexpression as a factor associated with a poor prognosis (P=.047). Patients with MGC who had a predominance of signet ring cells in mucin pools had poorer disease-specific survival than patients who had MGC with predominant tubular differentiation (P=.017).

Conclusions: The clinicopathologic and molecular characteristics of MGCs differed from those of NMGCs. Furthermore, the results indicated that EGFR overexpression and histologic subtyping by predominant tumor cell type in mucin pools may be helpful for predicting clinical outcome in patients with MGC.