ASSESSMENT OF EGFR AND TGF-ALPHA EXPRESSION IN RELATIONSHIP TO HPV STATUS AND KI-67 DISTRIBUTION IN CERVICAL INTRAEPITHELIAL NEOPLASMS

Expression of epidermal-growth-factor receptor (EGFR), transforming gr owth factor alpha (TGF-alpha) and Ki-67 proliferation antigen in cervi cal intra-epithelial neoplasms were analyzed. To examine the interrela tionship of TGF-alpha, EGFR, Ki-67 and HPV status in dysplasia and car cinoma in situ, formalin-fixed tissue sections of 92 women were immuno stained with monoclonal antibodies to EGFR, TGF-alpha and Ki-67. The p resence of HPV was assessed by in situ DNA hybridization. The highest positive TGF-alpha expression was seen in the group of mild dysplasia. The difference was significant between the relatively high expression in mild dysplasia and the low occurrence in severe dysplasia and carc inoma in site as well. The same relation could be found between TGF-al pha expression in papilloma-virus-negative dysplasia and those with th e presence of HPV 16/18. In contrast to these findings, the Ki-67 prol iferation marker was intensely detectable in severe dysplasia and carc inoma in situ. Ki-67-stained neoplastic cell nuclei were found in a si gnificantly higher percentage of HPV-positive than in HPV-negative les ions. TGF-alpha over-expression is obviously combined with low prolife rating activity and vice verse. Irrespective of the grade of dysplasia or HPV status, EGFR was expressed abnormally as compared with normal squamous epithelium. Over-expression of TGF-alpha in mild dysplasia co uld be associated with the autocrine pathway of cell-growth regulation . In the presence of HPV 16/18 the EGFR/TGF-alpha pathway for growth s timulation is probably not involved. (C) 1996 Wiley-Liss, Inc.