title: Role of cyclin D1 amplification and expression in vulvar carcinomas.
abstract: Cyclin D1 (CCND1) belongs to the family of D-type cyclins involved in cell cycle progression, transcriptional regulation, and cell migration. CCND1 was found to be amplified and overexpressed in a variety of cancers, including some vulvar carcinoma cell lines. To determine the relationship of CCND1 copy number changes and CCND1 protein expression with clinicopathologic features and prognosis, 183 vulvar carcinomas were analyzed on a tissue microarray. Amplification was observed in 32 (22.4%) vulvar cancer specimens and was statistically related to the presence of regional lymph node metastases (P < .001). Detectable CCND1 expression was found in 139 (83.2%) of vulvar carcinomas, and 76 (45.5%) exhibited a moderate or strong expression. Increased levels of CCND1 expression were significantly related to higher patient age (P = .013), positive pN category (P = .004), and negative human papillomavirus status (P < .001). Basaloid as well as verrucous, warty-type, and mixed vulvar carcinomas showed lower CCND1 expression levels than keratinizing or nonkeratinizing tumors (P < .001 and P = .032, respectively). Elevated CCND1 expression levels and amplification of the CCND1 gene were closely connected in the present analysis (P < .001). Patient prognosis was independent from CCND1 amplification status and expression level (P = .57 each). In conclusion, CCND1 is amplified and overexpressed in a substantial proportion of vulvar carcinomas and associated with the occurrence of locoregional lymph node metastases, especially in human papillomavirus-negative tumors.
authors.affiliation: Institute of Pathology, University Medical Centre Hamburg-Eppendorf, Hamburg 20246, Germany. mchoschz@uke.uni-hamburg.de
authors.forename: Matthias
authors.initials: M
authors.lastname: Choschzick
authors.forename: Stephan
authors.initials: S
authors.lastname: Hess
authors.forename: Pierre
authors.initials: P
authors.lastname: Tennstedt
authors.forename: Frederik
authors.initials: F
authors.lastname: Holst
authors.forename: Hiltila
authors.initials: H
authors.lastname: Bohlken
authors.forename: Frederike
authors.initials: F
authors.lastname: Gieseking
authors.forename: Sven
authors.initials: S
authors.lastname: Mahner
authors.forename: Linn
authors.initials: L
authors.lastname: Woelber
authors.forename: Ronald
authors.initials: R
authors.lastname: Simon
authors.forename: Guido
authors.initials: G
authors.lastname: Sauter
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019938:Cyclin D1 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005784:Gene Amplification; D006801:Humans; D008207:Lymphatic Metastasis / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D011379:Prognosis; D014844:Vulva / Q000378:metabolism / Q000473:pathology; D014846:Vulvar Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D019938:Cyclin D1