Claudin expression in pancreatic endocrine tumors as compared with ductal adenocarcinomas

Abstract

Altered expression of recently described claudins (CLDNs) as members of tight junction (TJ) transmembrane proteins was noted in several malignancies. We aimed to analyze protein and messenger RNA (mRNA) expressions of different CLDNs in human pancreatic endocrine tumors (PET) and ductal adenocarcinomas. A total of 45 formalin-fixed, paraffin-embedded samples were studied. Immunohistochemistry and real-time reverse transcriptase polymerase chain reaction analysis were carried out for quantification of CLDN 1, -2, -3, -4, and -7 expressions. Normal acini and ducts showed strong CLDNs 1, -3, -4, and -7 and scattered CLDN 2 protein expressions, while Langerhans islands revealed only CLDN 3 and -7 expressions. CLDN 2 expression was found in the half of ductal adenocarcinomas, while the vast majority of endocrine tumors were negative. CLDN 1, -4, and -7 immunohistochemistry was positive in all adenocarcinomas, whereas endocrine tumors were completely negative for CLDNs 1 and -4. CLDN 3 and -7 proteins were detected in all endocrine tumors, while CLDN 3 in ductal adenocarcinomas was negative. The mRNA expression of CLDNs showed differences between endocrine tumors and ductal adenocarcinomas, similar as found for protein expression. Our findings support that PET and ductal carcinomas are specifically characterized by different expression pattern of CLDNs. High expressions of CLDN 3 in endocrine tumors and CLDN 4 in ductal carcinomas might attract them as targets for adjuvant therapy.