title: Allelic imbalance in lichen sclerosus, hyperplasia, and intraepithelial neoplasia of the vulva.
abstract: BACKGROUND
  Few studies have addressed in detail the genetic alterations that occur in vulvar squamous carcinomas (VSCC) and their precursor lesions. In a previous study, we determined the most common chromosomal loci for allelic imbalance (AI) in HPV-positive and -negative VSCCs. The present study was designed to determine whether AI and the microsatellite instability phenotype (MIN) were present in epithelial lesions known to be associated with VSCC.
  
  
  METHODS
  Fifty-seven epithelial loci were analyzed, including HPV-positive (classic) and -negative (differentiated) vulvar intraepithelial neoplasms (VINs), lichen sclerosus (LS), and nonatypical hyperplasias. Thirty-one epithelial loci (55%) were obtained from patients with associated invasive vulvar carcinoma. HPV status was determined by polymerase chain reaction analysis. AI and MIN were determined by comparisons of microdissected target tissues with stromal controls, targeting 11 chromosomal loci.
  
  
  RESULTS
  AI was identified in all epithelial categories, involving at least one chromosomal locus in 67, 53, 50, and 43% of classic VIN, differentiated VIN, hyperplasia, and LS. MIN was infrequent (10-13%), but confined to HPV-negative epithelial changes. HPV-positive lesions generally scored for AI more frequently, but certain loci scored nearly equally in both HPV-positive and -negative lesions, including 8p, 11q, and 17p. There were no differences in frequency of AI between epithelia with and without associated invasive carcinoma.
  
  
  CONCLUSIONS
  The presence of allelic imbalance in vulvar hyperplasia and LS supports the hypothesis that these alterations are at greater risk for neoplasia despite the absence of conspicuous cellular atypia. A model is proposed in which these changes represent monoclonal expansion and are at empirically greater risk for subsequent "critical events" leading to morphologic atypia (VIN). The possibility that these early genetic changes influence both HPV-positive and -negative pathways merits further study.
authors.affiliation: Division of Women's and Perinatal Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: A P
authors.initials: AP
authors.lastname: Pinto
authors.forename: M C
authors.initials: MC
authors.lastname: Lin
authors.forename: E E
authors.initials: EE
authors.lastname: Sheets
authors.forename: M G
authors.initials: MG
authors.lastname: Muto
authors.forename: D
authors.initials: D
authors.lastname: Sun
authors.forename: C P
authors.initials: CP
authors.lastname: Crum
mesh_terms: D002278:Carcinoma in Situ / Q000235:genetics* / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D006801:Humans; D006965:Hyperplasia / Q000235:genetics; D018459:Lichen Sclerosus et Atrophicus / Q000235:genetics*; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats / Q000235:genetics*; D009361:Neoplasm Invasiveness; D011230:Precancerous Conditions / Q000235:genetics; D018570:Risk Assessment; D014844:Vulva / Q000473:pathology*; D014846:Vulvar Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D004273:DNA, Neoplasm