Clinical implications of luminal membrane expression of mesothelin in intraductal papillary mucinous neoplasms.

Abstract

179 Background: We recently explored that the expression of mesothelin was related to an unfavourable patient outcome in pancreatic cancer. Furthermore, in gastric cancer, we investigated that the luminal membrane expression of mesothelin was a reliable prognostic factor. Intraductal papillary mucinous neoplasms (IPMNs) often exhibit a spectrum of dysplasia ranging from adenoma to carcinoma in the same lesions. Therefore, we investigated the immunohistochemical analysis of mesothelin expression in IPMNs, especially focusing on the localization of mesothelin. Methods: Tissue samples from37 IPMNs were immunohistochemically examined. The types of IPMNs were classified into 2 groups: low, intermediate and high-grade dysplasia (L-H grade dysplasia) and IPMN with an associated invasive carcinoma (Invasive carcinoma). The proportion and intensity of constituent tumor cells with mesothelin expression were analyzed and classified as positive expression or negative expression. Furthermore, among the ‘mesothelin-positive’ cases, the staining localisation of mesothelin was evaluated as ‘luminal membrane positive’ and/or ‘cytoplasmic positive’. Results: In 37 cases of IPMNs, mesothelin expression was observed in 21 cases (56.8%), 46.2% (12 of 26) of L-H grade dysplasia and 81.8% (9 of 11) of Invasive carcinoma; p=0.071. Luminal membrane positive was observed in 10 cases (27%), 18.2% (4 of 22) of L-H grade dysplasia and 21% (6 of 11) of Invasive carcinoma; p=0.00016. Cytoplasmic positive was observed in 17 cases (27.0%), 38.5% (10 of 26) of L-H grade dysplasia and 63.6% (7 of 11) of Invasive carcinoma; p=0.28. Among 37 IPMNs, 6 cases showed recurrence after surgery. Five cases exhibited mesothelin expression, and all 5 cases exhibited luminal membrane positive. Conclusions: we demonstrated the clinicopathological significance of the luminal membrane expression of mesothelin in IPMNs. The immunohistochemical examination of mesothelin expression should be clinically useful for prognostication and for decision making about further treatment procedures after surgical therapy in patients with IPMNs.