title: 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.
authors.affiliation: Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
authors.forename: Jin Ha
authors.initials: JH
authors.lastname: Lee
authors.forename: Kyung Sik
authors.initials: KS
authors.lastname: Kim
authors.forename: Tae-Jung
authors.initials: TJ
authors.lastname: Kim
authors.forename: Sung Pil
authors.initials: SP
authors.lastname: Hong
authors.forename: Si Young
authors.initials: SY
authors.lastname: Song
authors.forename: Jae Bock
authors.initials: JB
authors.lastname: Chung
authors.forename: Seung Woo
authors.initials: SW
authors.lastname: Park
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000378:metabolism* / Q000473:pathology; D000236:Adenoma / Q000378:metabolism / Q000473:pathology; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism* / Q000473:pathology; D002291:Carcinoma, Papillary / Q000378:metabolism* / Q000473:pathology; D062506:Claudin-4; D057167:Claudins; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D015996:Survival Rate
chemical_list: C486683:CLDN18 protein, human; C491875:CLDN2 protein, human; C568157:CLDN4 protein, human; D062506:Claudin-4; D057167:Claudins; D008565:Membrane Proteins