Comparative study of invasive squamous cell carcinoma and verrucous carcinoma of the oral cavity: expression of bcl-2, p53, and Her-2/neu, and indexes of cell turnover.

Significant clinical and biological differences are found between invasive squamous cell carcinoma (SCCA) and verrucous carcinoma (VC) of the oral cavity. The correct diagnosis of these tumors has important therapeutic implications. Immunoperoxidase stains for bcl-2, p53, and Her-2/neu, and in situ end-labeling of DNA to identify apoptosis were performed in eight VC and eight SCCA matched for age, sex, and stage. Marked differences were identified in the pattern of expression of oncogenes and the indexes of cell turnover in these two types of tumors. VC displayed minimal apoptosis in rare keratinizing cells (0 to 3%); p53-positive cells (4/8) and Ki-67 (8/8) were confined to the nuclei of the basal proliferating layers; and bcl-2 (4/8) was expressed only in the cytoplasm of rare tumor cells. In contrast, SCCA displayed higher apoptosis rates (5 to 10%), whereas p53- (5/8) and Ki-67- (8/8) positive nuclei were distributed randomly throughout the tumor. Very well differentiated areas in one SCCA case had a pattern of staining for p53 and Ki-67 similar to the one seen in VC. In SCCA bcl-2 showed patchy cytoplasmic staining (4/8) or strong cytoplasmic and nuclear positivity (2/8) in the less differentiated tumors. Her-2/neu was negative in all VC and SCCA cases. The different levels and patterns of gene expression and cell turnover between SCCA and VC undoubtedly correlate with the different biology and prognosis of these tumors.