Distribution of TPA and cytokeratins in gastrointestinal carcinomas as revealed by immunohistochemistry

Abstract

The presence and distribution of tissue polypeptide antigen (TPA) were assessed in gastrointestinal carcinomas of different origin, morphology and degree of differentiation. Immunocytochemistry was employed, using the PAP technique on formalin-fixed, paraffin-embedded material and compared with the results obtained with antibodies to cytokeratins. Like cytokeratins, TPA was a reliable marker of epithelial differentiation and showed tissue distribution patterns similar to cytokeratins, as revealed by antibodies with broad-range cytokeratin immunoreactivity. In most carcinomas, TPA-specific immunostaining was less intense than in non-neoplastic tissue. No direct relationship between intensity of TPA staining and morphological degree of differentiation and proliferation was found. TPA staining was most pronounced at the periphery of the cells. In stratified epithelium, i.e. oesophageal mucosa, basally located cells exceeded superficial cells in TPA immunoreactivity in contrast to the cytokeratin antibodies which decorated the more superficially placed cell layers. TPA and cytokeratin staining patterns were similar in neoplastic and non-neoplastic gastric, intestinal mucosa, as well as in biliary tract epithelium. Antral and cardial mucoid glands of the stomach as well as gastric carcinomas of the pylorocardial type remained unstained with both types of antibodies. Similar staining with TPA and cytokeratin antibodies was also observed in pancreatic and liver tissue. In this study, hepatocytes were, although weakly, stained by TPA antibodies and an identical staining was found with benign and malignant hepatocellular neoplasms. Ductal and ductular TPA-staining was most conspicuous and so was the immunoreactivity of cholangiocellular carcinomas. A comparison between TPA and cytokeratins was also made by immunoblotting which revealed immunoreactivity of antibodies to TPA with cytokeratin polypeptides of different species (man, mouse) and organs (epidermis, liver), particularly with the cytokeratin component 8 of human liver and the related component A of mouse liver. The significance of this finding is uncertain until the pertinent epitopes have been revealed by monoclonal mapping of the components which exhibit similar molecular weights by SDS polyacrylamide gel electrophoresis.