A panel of p16INK4A, MIB1 and p53 proteins can distinguish between the 2 pathways leading to vulvar squamous cell carcinoma

• Published in: International journal of cancer Vol. 123; no. 12; pp. 2767 - 2773
• Main Authors: Hoevenaars, Brigiet M., van der Avoort, Irene A.M., de Wilde, Peter C.M., Massuger, Leon F.A.G., Melchers, Willem J.G., de Hullu, Joanne A., Bulten, Johan
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 15-12-2008; Wiley-Liss
• Subjects: Biological and medical sciences; Female genital diseases; Gynecology. Andrology. Obstetrics; HPV; Medical sciences; MIB1; p16INK4A; p53; Tumors; vulvar carcinoma; vulvar intraepithelial neoplasia; Cell proliferation; Vulvar intraepithelial neoplasia; Biological marker; Vulva squamous cell carcinoma; Papovaviridae; Vulva carcinoma; Carcinogenesis; CDKN2 gene; HPV; Papillomavirus; Human papillomavirus; Cancerology; TP53 Gene; Tumor suppressor gene; Human; vulvar carcinoma; Premalignant lesion; Malignant tumor; Female genital diseases; Virus; p53: MIB1; Ki67 antigen; Vulvar diseases; p16INK4A; Cancer
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.23857

Two pathways leading to vulvar squamous cell carcinoma (SCC) exist. The expression of proliferation‐ and cell‐cycle‐related biomarkers and the presence of high‐risk (hr) HPV might be helpful to distinguish the premalignancies in both pathways. Seventy‐five differentiated vulvar intra‐epithelial neoplasia (VIN)‐lesions with adjacent SCC and 45 usual VIN‐lesions (32 solitary and 13 with adjacent SCC) were selected, and tested for hr‐HPV DNA, using a broad‐spectrum HPV detection/genotyping assay (SPF10‐LiPA), and the immunohistochemical expression of MIB1, p16INK4A and p53. All differentiated VIN‐lesions were hr‐HPV‐ and p16‐negative and in 96% MIB1‐expression was confined to the parabasal layers. Eighty‐four percent exhibited high p53 labeling indices, sometimes with parabasal extension. Eighty percent of all usual VIN‐lesions were hr‐HPV‐positive, p16‐positive, MIB1‐positive and p53‐negative. Five (of seven) HPV‐negative usual VIN lesions, had an expression pattern like the other HPV‐positive usual VIN lesions. In conclusion, both pathways leading to vulvar SCC have their own immunohistochemical profile, which can be used to distinguish the 2 types of VIN, but cannot explain differences in malignant potential. © 2008 Wiley‐Liss, Inc.