title: MIB1 expression in basal cell layer: a diagnostic tool to identify premalignancies of the vulva.
abstract: Lichen sclerosus, high-grade usual vulvar intraepithelial neoplasia (VIN) and differentiated VIN have a different malignant potential. The objective of this study was to quantify the proliferative activity in the basal region of the epithelium of vulvar premalignancies. Furthermore, we investigated whether MIB1 expression in the basal region of vulvar epithelium can be helpful in diagnosing differentiated VIN, which may be hard to discern from normal epithelium. MIB1 was used to immunohistochemically visualise proliferating cells within formalin-fixed, paraffin-embedded, archival tissue sections of different vulvar premalignancies (N=48) and normal vulvar epithelium (N=16). Automatic digital image analysis software was developed to quantify the proliferating fraction in different parts of the epithelium (MIB1 positivity index). MIB1 expression differed among the various vulvar premalignancies; a MIB1-negative basal cell layer was a distinct feature of normal vulvar epithelium. No MIB1-negative basal cell layer was noted in differentiated VIN or other vulvar premalignancies. Owing to this negative cell layer, the MIB1 proliferation index in normal vulvar epithelium was significantly lower than in vulvar premalignancies. In conclusion, MIB1 expression can be a helpful tool in diagnosing a premalignancy and has additional value especially to distinguish differentiated VIN neoplasia from normal vulvar epithelium, but cannot explain the differences in malignant potential.
authors.affiliation: Department of Obstetrics & Gynaecology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. i.vanderavoort@obgyn.umcn.nl
authors.forename: Irene A M
authors.initials: IA
authors.lastname: van der Avoort
authors.forename: Jeroen A W M
authors.initials: JA
authors.lastname: van der Laak
authors.forename: Ard
authors.initials: A
authors.lastname: Paffen
authors.forename: Johanna M M
authors.initials: JM
authors.lastname: Grefte
authors.forename: Leon F A G
authors.initials: LF
authors.lastname: Massuger
authors.forename: Peter C M
authors.initials: PC
authors.lastname: de Wilde
authors.forename: Joanne A
authors.initials: JA
authors.lastname: de Hullu
authors.forename: Johan
authors.initials: J
authors.lastname: Bulten
mesh_terms: D002278:Carcinoma in Situ / Q000378:metabolism / Q000473:pathology; D003937:Diagnosis, Differential; D004847:Epithelial Cells / Q000737:chemistry / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D018459:Lichen Sclerosus et Atrophicus / Q000378:metabolism / Q000473:pathology; D011230:Precancerous Conditions / Q000175:diagnosis* / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000096:biosynthesis*; D014844:Vulva / Q000737:chemistry / Q000473:pathology*; D014846:Vulvar Neoplasms / Q000175:diagnosis* / Q000378:metabolism
chemical_list: C513496:MIB1 ligase, human; D044767:Ubiquitin-Protein Ligases