Immunohistochemical expression of Mdm2 and p53 in penile verrucous carcinoma.

Verrucous carcinoma (VC) of the penis is an uncommon squamous tumor that pursues a biologically indolent course. Unlike conventional squamous cell carcinoma (SCC) of the penis, pathogenic roles for human papillomavirus (HPV) infection and p53 mutation have not been reported in VC. We compared the immunohistochemical expression of Mdm2 and p53 in 7 cases of VC and 7 cases of SCC. The Mdm2 gene product preferentially labeled the perinuclear membrane in the granular layer of VC tumor cells, whereas SCC cases showed weak, focal, cytoplasmic staining for Mdm2. The mean labeling index for Mdm2 was higher in VC compared to SCC [79.3 (SE +/- 7.2) in VC vs 18.3 (SE +/- 2.4) in SCC, p < 0.001]. In SCC cases, the normal surrounding skin showed mild granular-layer staining and dysplastic foci that failed to stain with Mdm2 antibody. Weak p53 immunolabeling was seen within nuclei of scattered tumor cells in the cases of VC, whereas the SCC cases showed strong nuclear staining of p53 throughout the tumors. The mean labeling index for p53 was lower in VC compared to SCC [24.8 (SE +/- 3.9) in VC vs 64.7 (SE +/- 9.0) in SCC, p < 0.01]. In SCC cases, the normal surrounding skin showed moderate staining for p53, preferentially confined to the basal layer. Dysplastic foci in the cases of SCC showed increased p53 labeling. In summary, immunohistochemical analysis showed significantly different levels of expression of Mdm2 and p53 in penile VC vs SCC. Overexpression of the Mdm2 gene product may be important in the pathogenesis of VC. Since Mdm2 is a negative regulator of p53, overexpression of Mdm2 may explain why p53 is down-regulated and, therefore, permissive to oncogenic transformation.