Immunohistochemical localization of ras p21 and carcinoembryonic antigens (CEA) in cholangiocarcinoma.

An expression of ras p21 proteins on cholangiocarcinoma (CC) (intrahepatic bile duct carcinoma) cells was examined by an immunoperoxidase method using an appropriate dilution of mouse monoclonal antibody RAP-5, with which no positive staining was obtained in livers with normal histology. Of 44 CCs examined 39 were positive for the antigens; well-differentiated adenocarcinoma usually showed a diffuse weak, cytoplasmic staining in nearly all tumor cells with the same staining intensity, while in moderately and poorly differentiated adenocarcinoma the expression of p21 varied markedly in intensity from cell to cell in the same cell nest. The number of positive cells decreased with the grade of tumor, and no or little staining was observed in undifferentiated areas. These findings indicate that the expression of ras p21 antigens was lost with increasing dedifferentiation of tumor cells. Carcinoembryonic antigens (CEA) were positive in 42 of 44 CCS. Well-differentiated adenocarcinoma expressed CEA along the apical surfaces of the tumor glands. With the dedifferentiation of tumor cells, the expression of CEA became prominent not only at the apical surfaces but also on the basolateral surfaces and in the cytoplasms, and further in the surrounding stromal tissue. There was no clear-cut correlation between the expression of p21 antigens and the production of CEA in CCs.