title: A panel of p16(INK4A), MIB1 and p53 proteins can distinguish between the 2 pathways leading to vulvar squamous cell carcinoma.
abstract: 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 (SPF(10)-LiPA), and the immunohistochemical expression of MIB1, p16(INK4A) 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.
authors.affiliation: Department of Pathology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Brigiet M
authors.initials: BM
authors.lastname: Hoevenaars
authors.forename: Irene A M
authors.initials: IA
authors.lastname: van der Avoort
authors.forename: Peter C M
authors.initials: PC
authors.lastname: de Wilde
authors.forename: Leon F A G
authors.initials: LF
authors.lastname: Massuger
authors.forename: Willem J G
authors.initials: WJ
authors.lastname: Melchers
authors.forename: Joanne A
authors.initials: JA
authors.lastname: de Hullu
authors.forename: Johan
authors.initials: J
authors.lastname: Bulten
mesh_terms: D000328:Adult; D000368:Aged; D052685:Alphapapillomavirus / Q000235:genetics / Q000302:isolation & purification; D014408:Biomarkers, Tumor / Q000032:analysis*; D002278:Carcinoma in Situ / Q000737:chemistry / Q000175:diagnosis; D002294:Carcinoma, Squamous Cell / Q000737:chemistry* / Q000175:diagnosis* / Q000473:pathology / Q000821:virology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis*; D004279:DNA, Viral / Q000302:isolation & purification; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000150:complications; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*; D014412:Tumor Virus Infections / Q000150:complications; D044767:Ubiquitin-Protein Ligases / Q000032:analysis*; D014846:Vulvar Neoplasms / Q000737:chemistry* / Q000175:diagnosis* / Q000473:pathology / Q000821:virology
chemical_list: D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral; D016159:Tumor Suppressor Protein p53; C513496:MIB1 ligase, human; D044767:Ubiquitin-Protein Ligases