Immunohistochemical analysis of claudin expression in pancreatic cystic tumors

Abstract

Aberrant expression of the claudin family of proteins has been reported in many human cancers, including pancreatic ductal carcinoma. Intraductal papillary mucinous neoplasms of the pancreas (IPMN) and mucinous cystic neoplasms (MCN) are considered precancerous lesions that are able to progress towards pancreatic ductal adenocarcinoma. We analyzed the expression of several claudin family members using surgical IPMN and MCN specimens to clarify the relationships between claudin expression and clinicopathological features. Twenty-nine and 25 consecutive cases of IPMN and MCN were selected and the expression of claudin-2, -4 and -18 was analyzed by immunohistochemistry. In addition, IPMN and MCN histological grade as well as IPMN subtypes were analyzed in relation to claudin expression. The 29 cases of IPMN comprised of 3 (10.3%) adenomas, 18 (62.1%) borderline malignancies and 8 (27.6%) carcinomas. The 25 cases of MCN comprised of 13 (52%) adenomas, 5 (20%) borderline malignancies and 7 (28%) carcinomas. Claudin-2, -4 and -18 showed strong expression both in IPMN and MCN, with the exception of claudin-4 in MCN. The expression grades of claudin-2 in both IPMN and MCN became weaker with increased histological grade. On the other hand, the expression grades of claudin-4 and -18 became stronger with increased histological grade in both IPMN and MCN. With regard to histological subtype, claudin-4 expression was the strongest in pancreatobiliary type IPMN, and claudin-18 expression was the strongest in gastric type IPMN. The distinct expression patterns of claudin-2, -4 and -18 suggest that claudins may serve as useful molecular markers for tumor differentiation and progression in IPMN and MCN.