Alterations of the p16INK4a/Rb/cyclin-D1 pathway in vulvar carcinoma, vulvar intraepithelial neoplasia, and lichen sclerosus

Enrique Lerma, Manel Esteller, James G. Herman, Jaime Prat

Research output: Contribution to journalArticle

Abstract

Three different alterations in the p16/pRb/cyclin-D1 pathway (p16INK4a-promoter hypermethylation and expression of pRb and cyclin-D1) were investigated in a series of 38 cases of vulvar carcinoma (VC), 13 cases of vulvar intraepithelial neoplasia (VIN), and 21 cases of lichen sclerosus (LS). Paraffin blocks from 72 patients were selected for investigation of DNA methylation patterns in the CpG island of p16INK4a by methylation-specific polymerase chain reaction. Immunohistochemical studies for pRb and cyclin-D1 were performed using the standard avidin-biotin-peroxidase complex method. Epigenetic silencing of p16INK4a was detected in 68% of VC, 69.2% of VIN, and 42.8% of LS cases. Lack of pRb protein was found in 21% of VC, 0% of VIN, and 0% of LS cases. Overexpression of cyclin-D1 was found in 21% of VC, 30.8% of VIN, and 0% of LS cases. We conclude (1) that p16INK4a epigenetic inactivation most likely represents an early event, insufficient for malignant transformation, that may occur in clinically benign lesions such as LS; (2) that lack of pRb was only detected in fewer than one quarter of the carcinomas and could be considered a late secondary event; and (3) that cyclin-D1, which was overexpressed in VC and VIN, could contribute to the malignant transformation in association with p16 hypermethylation.

Original languageEnglish (US)
Pages (from-to)1120-1125
Number of pages6
JournalHuman Pathology
Volume33
Issue number11
DOIs
StatePublished - Nov 1 2002

Keywords

  • Cell cycle
  • Cyclin D1
  • Hypermethylation
  • Lichen sclerosus
  • P16
  • pRb
  • Squamous cell carcinoma
  • Vulva
  • Vulvar intraepithelial neoplasia
  • Vulvar neoplasia

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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