Changing patterns and re-distribution of antigen in poorly differentiated carcinomas: its implications in tumour diagnosis

The variability of expression of tumour-associated antigens via either antigenic heterogeneity or antigenic modulation presents a basic problem in immunohistochemical diagnosis of poorly/undifferentiated tumours. This work was designed to study antigenic expression on human resected epithelial tumours by a panel of most widely used antibodies (EMA, CEA, AUAI & Cytokeratin) in relation to tumour differentiation and polarization. It was observed that poorly differentiated carcinoma with loss of polarity show homogeneous membrane staining (with antibodies against EMA, CEA & AUAI) in contrast to either apical (luminal) or basolateral membrane staining in well differentiated counterparts. Biochemical studies have shown that apical and basolateral epithelial cell membrane domains have a characteristic set of glycoproteins. Tight junctions are essential for maintaining this functional polarization. It was concluded that structural and functional abnormalities of tight junctions in poorly differentiated carcinomas results in loss of polarity with progressive invasion of the cell surface by antigenic glycoprotein and resultant homogeneous individual cell antigenic expression in poorly differentiated carcinomas. This study demonstrates that antigenic expression on tumour cells is not static, but dynamic and heterogeneity of antigenic expression may well be due to biological factors such as spatial configuration of the lesion