title: Immunohistochemical patterns of ProEx C in vulvar squamous lesions: detection of overexpression of MCM2 and TOP2A.
abstract: Two major subtypes of vulvar squamous cell carcinomas (SCC) have been described. Basaloid and warty SCC are human papillomavirus-related and associated with classic vulvar intraepithelial neoplasia (VIN). Keratinizing SCC is associated with lichen sclerosus and differentiated VIN, but not with human papillomavirus. This study was undertaken to examine the expression patterns of ProEx C in vulvar SCC and its precursors. We analyzed 22 cases with normal vulvar epidermis, 13 cases of lichen sclerosus, 14 cases of condylomas, 23 cases of high-grade classic VIN, 6 cases of differentiated VIN, 3 cases of verrucous carcinomas, 10 cases of keratinizing SCC, and 8 cases of basaloid and warty SCC. ProEx C targets minichromosome maintenance protein and topoisomerase II alpha protein which are overexpressed in the cell nucleus during aberrant S-phase induction. Marked confluent ProEx C expression is present in high-grade classic VIN with nuclear staining extending into the middle and upper layers of the epidermis. Condylomas show parabasal nuclear immunoreactivity associated with scattered ProEx C-positive nuclei in the more differentiated suprabasilar layers. Invasive SCC shows variable staining patterns. In contrast, ProEx C staining is essentially limited to the basal and parabasal layers in normal epidermis, lichen sclerosus, differentiated VIN, and verrucous carcinoma. Overall, ProEx C is a useful proliferation marker for high-grade VIN analogous to the staining patterns reported in high-grade cervical intraepithelial neoplasia.
authors.affiliation: Department of Pathology, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.forename: Jorge L
authors.initials: JL
authors.lastname: Gonzalez
authors.forename: Jeoffry B
authors.initials: JB
authors.lastname: Brennick
authors.forename: Miaoliang
authors.initials: M
authors.lastname: Liu
authors.forename: Shaofeng
authors.initials: S
authors.lastname: Yan
mesh_terms: D000951:Antigens, Neoplasm / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D003218:Condylomata Acuminata / Q000378:metabolism / Q000473:pathology; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D064111:Minichromosome Maintenance Complex Component 2; D009687:Nuclear Proteins / Q000378:metabolism*; D000075223:Poly-ADP-Ribose Binding Proteins; D007724:Vulvar Lichen Sclerosus / Q000378:metabolism / Q000473:pathology; D014846:Vulvar Neoplasms / Q000378:metabolism* / Q000473:pathology; D002578:Uterine Cervical Dysplasia / Q000378:metabolism / Q000473:pathology
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; C084859:MCM2 protein, human; D064111:Minichromosome Maintenance Complex Component 2; D004250:DNA Topoisomerases, Type II; C000618811:TOP2A protein, human