P53 expression in vulvar carcinoma, vulvar intraepithelial neoplasia, squamous cell hyperplasia and lichen sclerosus.

BACKGROUND: p53 inactivation due to oncogenic viral proteins or mutations is an important molecular mechanism in carcinogenesis, which has also been demonstrated for vulvar carcinoma. To evaluate p53 changes in vulvar carcinogenesis, we analyzed p53 expression in vulvar carcinoma, vulvar intraepithelial neoplasia (VIN), lichen sclerosus (LS) and squamous cell hyperplasia (SH). PATIENTS AND METHODS: Seventy-three carcinomas, 141 cases of VIN, 55 biopsies of LS with 8 associated to carcinoma, 57 cases of SH with 14 associated to carcinoma and 10 cases without neoplastic changes were stained immunohistologically for p53. The pattern, intensity and number of stained cells were analyzed. Results were compared to p53 expression in vulvar epithelium without neoplastic changes and analyzed statistically by chi2-test.
RESULTS: Normal vulvar epithelium showed low p53 staining in the basal epithelial layers. Forty % of LS and SH not associated to carcinoma showed immunohistological signs of p53 mutation, while cases associated with carcinoma did so in 90%. In VIN, p53 was predominantly overexpressed in the differentiated subtype. Sixty-seven % of the carcinomas showed immunohistological changes of p53 expression. Tumors with low p53 expression were significantly associated with patients younger than 50 years (p<0.01) and basaloid or condylomatous tumor type (p<0.015). There were three different patterns of p53 staining, which were significantly correlated with tumor type (p<0.01).
CONCLUSION: p53 mutations are present in typical keratinizing carcinomas, precursor lesions and disorders with elevated risk for vulvar cancer. Thus, p53 mutation seems to occur early in vulvar carcinogenesis and may become a useful marker, especially in lesions with increased risk of carcinoma.