p53 Expression in Vulvar Carcinoma, Vulvar Intraepithelial Neoplasia, Squamous Cell Hyperplasia and Lichen Sclerosus PEER HANTSCHMANN1, SONJA STERZER2, UDO JESCHKE2 and KLAUS FRIESE2 1Department 2I.
of Gynecology and Obstetrics, Kreisklinik Altötting, 84503 Altötting; Frauenklinik, Klinikum Innenstadt, LMU-München, Germany
Abstract. 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 Ã2-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 (p25%
X2-test
Age 60
2 15
0 5
2 30
ns
2 12
3 12
0 44
p25% versus 1-25%. (2)0-25%
42 (58%) expressed p53 with moderate or strong intensity (Table I). Tumors with >10% p53-positive cells showed nuclear staining in three different patterns in the context of tumor architecture (Table II). Thirty-two % were stained predominantly in the basal parts of infiltrating tumor aggregates (basal type) (Figure 1a) and 9% at the infiltrating tumor border (infiltrating type) (Figure 1b). In 59%, stained nuclei were not restricted to special areas (diffuse type) (Figure 1c). The diffuse type was significantly associated with the basaloid and condylomatous tumor type (p
