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Background: Mesothelin (MSN) is expressed both in normal mesothelium and in several types of malignant tumors. In recent literature there are conflicting results on the role of MSN expression in gastric cancer. In this study we evaluated the clinicopathological and prognostic significance of MSN expression in gastric and gastro-esophageal junction (GEJ) cancer.
Methods: Tissue specimens from 104 gastric and GEJ cancer patients who were submitted to surgical resection in our institution were immunohistochemically evaluated. The intensity of MSN expression in tumor cells was analyzed and the location of immunostaining was classified into membrane and/or cytoplasmic expression.
Results: MSN was positive in 42 (40.4%) cases and MSN expression was correlated with tumor location (61.3% of GEJ cancers), macroscopic appearance (48,8% of fungating and ulcer-fungating tumors), Lauren histological classification (52% of intestinal type tumors), tumor invasion depth (pT, 7th edition of TNM classification) [57.5% of T4a tumors], lymph-node metastasis (pN) [46.3% of positive lymph node metastasis] and pathological stage. The cytoplasmic MSN expression, which was identified in 39 cases, was correlated with the same clinicopathological features of overall MSN expression and furthermore to the presence (41.1%) of lymphatic invasion. On the other hand, the membrane MSN expression was observed in 23 cases and was correlated only with tumor location and Lauren classification. For the survival analysis, only 89 cases of R0 resection were included (4 cases of gastric stump tumors were excluded of this analysis). The median follow-up of this group of patients was 20.5 (1-252) months (mos) and the median overall survival was 21 mos (5-year and 10-year survival were 32.5% and 30.7%, respectively). Despite that the survival curves according to MSN expression were different (18 vs. 34 mos; p=0.07), only the cytoplasmic MSN expression was significantly associated (p=0.024) to poorer survival (15 vs. 26 mos). Multivariate analysis revealed that cytoplasmic MSN expression was one of the independent prognostic factors (HR 1.769; 95% CI 1.00-3.13; p=0.05) together with pT, macroscopic appearance and venous invasion.
Conclusions: MSN expression in gastric and GEJ cancer was correlated with several clinicopathological features (namely GEJ location, fungating and ulcer-fungating tumors, intestinal type, serosal invasion, lymph node metastasis) and cytoplasmic MSN expression was an independent prognostic factor in R0 cases of our series.