Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
Oncol Rep. 2011 Apr;25(4):971-8. doi: 10.3892/or.2011.1132. Epub 2011 Jan 3.
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.
已有研究报道，Claudin 家族蛋白在多种人类癌症中表达异常，包括胰腺导管腺癌。胰腺导管内乳头状黏液性肿瘤（IPMN）和黏液性囊腺瘤（MCN）被认为是癌前病变，能够向胰腺导管腺癌进展。我们分析了外科手术切除的 IPMN 和 MCN 标本中几种 Claudin 家族成员的表达情况，以阐明 Claudin 表达与临床病理特征之间的关系。选择了 29 例连续的 IPMN 和 25 例 MCN 病例，并通过免疫组织化学分析 Claudin-2、-4 和 -18 的表达情况。此外，还分析了 IPMN 和 MCN 的组织学分级以及 IPMN 亚型与 Claudin 表达的关系。29 例 IPMN 包括 3 例（10.3%）腺瘤、18 例（62.1%）交界性肿瘤和 8 例（27.6%）癌。25 例 MCN 包括 13 例（52%）腺瘤、5 例（20%）交界性肿瘤和 7 例（28%）癌。Claudin-2、-4 和 -18 在 IPMN 和 MCN 中均表现出强表达，除了 MCN 中的 Claudin-4。随着组织学分级的增加，IPMN 和 MCN 中 Claudin-2 的表达分级变得更弱。另一方面，随着组织学分级的增加，IPMN 和 MCN 中 Claudin-4 和 -18 的表达分级变得更强。在组织学亚型方面，Claudin-4 在胰胆管型 IPMN 中表达最强，Claudin-18 在胃型 IPMN 中表达最强。Claudin-2、-4 和 -18 的表达模式明显不同，提示 Claudin 可能作为 IPMN 和 MCN 肿瘤分化和进展的有用分子标志物。
