Concordant p53 and mdm-2 protein expression in vulvar squamous cell carcinoma and adjacent lichen sclerosus

To determine if carcinogenic events in vulvar skin precede the onset of mor phologic atypia, the authors investigated for derangements in DNA content, cell proliferation, and cell death in vulvar carcinomas and surrounding ski n in 140 samples of tumor and surrounding skin collected from 35 consecutiv e vulvectomy specimen for squamous cell carcinoma (SCC) or vulvar intraepit helial neoplasia (VIN) 3. Vulvar non-cancer excisions were used as controls . Investigations consisted of histologic classification and measurement of 9 variables-epidermal thickness (acanthosis and rete ridge length), immunol abeling index (LI) for 3 proteins (p53 protein, Ki-67, and mdm-2), pattern of p53 expression (dispersed vs. compact), DNA content index, and presence of aneuploidy by image analysis and apoptotic rate by Apotag labeling. Sign ificant positive correlations were found for all nine variables studied ver sus increasing histologic severity in two proposed histologic stepwise mode ls of vulvar carcinogenesis (lichen sclerosus (LS) and VIN 3 undifferentiat ed associated SCC groups). High p53 LI (> 25) and the compact pattern of p5 3 expression (suspected oncoprotein) significantly correlated with LS and i ts associated vulvar samples compared with samples not associated with LS ( P less than or equal to 0.001). Furthermore, p53 LI, mdm-2 Li, and pattern of p53 expression were concordant between patient matched samples of LS and SCC. In addition, mdm-2 LI significantly correlated with dispersed pattern p53 LI suggesting a response to wildtype p53 protein accumulation. These f indings support the hypothesis that neoplastic transformation occurs in seq uential steps and compromises proteins involved in the cell cycle control. Concordance of p53 and mdm-2 protein expression in LS and adjacent SCC prov ides evidence that LS can act as a precursor lesion in the absence of morph ologic atypia. Overexpression of mdm-2 with stabilization and inactivation of p53 protein may provide an alternate pathway for vulvar carcinogenesis.