IMMUNOHISTOCHEMICAL STUDY OF METALLOTHIONEIN IN PANCREATIC CARCINOMAS

Metallothioneins are a family of intracellular metalloproteins that ha ve been thought to be involved in anticancer drug resistance. However, the role of metallothioneins in pancreatic cancer has not been invest igated in detail. The immunohistochemical localization of metallothion ein was examined in normal human adult pancreas tissue and in 75 pancr eatic duct cell carcinomas, using monoclonal anti-metallothionein anti body. Furthermore, in vitro studies on the sensitivity of pancreatic c ancer to cisplatin were performed in 10 cases of pancreatic carcinoma. Metallothionein staining was weakly positive in the acinar and islet cells and intralobular ducts but was negative in the large pancreatic ducts. In pancreatic carcinomas, metallothionein staining was diffusel y positive in 6 (8%), focally positive in 25 (33%) and negative in 44 (59%) of the 75 pancreatic carcinomas. The expression of metallothione ins in pancreatic tumors was related to metastasis, poor prognosis and poor histological grading (poorer glandular differentiation and nucle ar anaplasia). The in vitro study of tumor sensitivity to cisplatin sh owed no significant correlation between metallothionein expression and resistance to cisplatin. Metallothionein-positive pancreatic carcinom a will be potentially highly malignant or acquire an enhanced ability to produce metallothioneins as the malignant potential increases. The expression of metallothionein could be a prognostic indicator in pancr eatic carcinomas.