What does claudine-4 show on the papilla of Vater?

Introduction: Alterations in the papilla of Vater are major challenges for the pathologist. Accurate classification is especially important to determine the prognosis and choose the optimal therapy. Novel methods are to aid the pathologist. Tight junction proteins the claudines (CLDN) appear irregularly in tumorous processes. One of them, CLDN-4 is overexpressed in certain human tumors, like the cancer of the pancreas, bile ducts etc. The role of these proteins in tumorgenesis remains to be clarified, they seem to be worth to examine in cancer diagnostics.

Aim: We intended to perform a semiquantitative (scoring 1–3+) immunohistochemical testing of CLDN-4 in different diseases of the papilla of Vater. We compared our findings with the histological picture, and – in cases of tumors or tumor like lesions – with the phenotype. We do not know any previous study of the CLDN expression in the papilla of Vater.

Results: We examined 116 papilla biopsies in the last two years. Routine H&E staining revealed 75 inflammatory lesions, 21 cases of adenomatous hyperplasia, 20 neoplastic lesions, adenomas or carcinomas. In addition we reexamined some infiltrative carcinomas diagnosed in earlier periods. The inflammatory lesions were CLDN-4 negative, and the adenomatous hyperplasias showed focal, minimal positivity on the cell membranes in 2/21 cases. Tumors proved to be 2–3+ positive in 7/16 of the adenomas, while 100% of the infiltrative tumors – both intestinal and pancreato-biliary types – showed strong positive reaction on the cell membrane.

Conclusions: Investigation of CLDN-4 may be a valuable tool for the pathologist to define the biological behavior of a tumor like lesion. Since CLDN-4 is the receptor of the cytotoxic enterotoxin of Clostridium perfringens (CPE), tumors expressing this protein may be targets of CPE therapy, or future immunotherapies. This also underlines the importance of CLDN-4 determination.