IMMUNOHISTOCHEMICAL LOCALIZATION OF P53, PCNA, AND TGF-ALPHA PROTEINSIN FORMALDEHYDE-INDUCED RAT NASAL SQUAMOUS-CELL CARCINOMAS

Mutation of the p53 tumor suppressor gene is a common event in many hu man cancers and has been specifically associated with invasive squamou s cell carcinoma of the human skin and respiratory tract. Alterations in the p53 gene have also been identified in certain rodent tumors, in cluding formaldehyde-induced nasal squamous cell carcinomas. Overexpre ssion of transforming growth factor-alpha (TGF-alpha) is associated wi th carcinomas of the head and neck and respiratory tract in human pati ents and formaldehyde-induced rat nasal squamous cell carcinomas. Sect ions of rat noses containing tumors and other formaldehyde-induced les ions from rats exposed to 15 ppm formaldehyde vapor were examined usin g immunohistochemical techniques to detect and identify potential rela tionships between the presence and distribution of p53, proliferating cell nuclear antigen (PCNA), and TGF-alpha proteins. The five tumors t hat had p53 mutations were for mutant p53 protein by immunohistochemis try and three of six tumors with no detected p53 mutations were also i mmunoreactive for p53 protein. The presence, pattern, and distribution of p53 staining in tissue sections depended on the morphology of the lesion. PCNA immunoreactivity was strikingly similar in pattern and di stribution to p53 immunoreactivity, The pattern and distribution of im munoreactivity for TGF-alpha did not directly correlate with the other markers, Mutation of the p53 tumor suppressor gene may be an importan t step in the progression of formaldehyde-induced nasal carcinogenesis in the rat. This study demonstrated that immunohistochemistry is a us eful tool for the identification of sites within tumors that might hav e p53 mutations. (C) 1995 Academic Press, Inc.