title: Expression of human telomerase reverse transcriptase in vulvar intraepithelial neoplasia and squamous cell carcinoma: an immunohistochemical study with survivin and p53.
abstract: BACKGROUND
  Human telomerase reverse transcriptase (hTERT), an enzyme that enables cells to overcome replicative senescence and to divide indefinitely, is overexpressed in many cancers and their precursor lesions.
  
  
  OBJECTIVE
  To test whether hTERT expression is related to neoplastic progression and resistance to apoptosis in vulvar epithelia.
  
  
  METHODS
  Immunoexpression of hTERT was evaluated in 101 formalin-fixed, paraffin-embedded archival vulvar epithelia consisting of normal squamous vulvar epithelia (n  =  25), lichen sclerosus (n  =  10), high-grade classic vulvar intraepithelial neoplasia (n  =  16), differentiated vulvar intraepithelial neoplasia (n  =  18), and vulvar invasive keratinizing squamous cell carcinoma (n  =  32) and related to survivin and p53 expression. Immunostaining for all factors was scored for moderate and strong intensities with regard to quantity to determine upregulation and overexpression (score 0, 0% immunoreactive cells; score 1+, <5% immunoreactive cells; score 2+, 5% to 50% immunoreactive cells; score 3+, >50% immunoreactive cells). Score 3+ was considered as overexpression.
  
  
  RESULTS
  Nuclear hTERT immunoexpression was closely related to survivin reactivity, increased from normal vulvar squamous epithelia to lichen sclerosus and to high-grade classic vulvar intraepithelial neoplasia, differentiated vulvar intraepithelial neoplasia, and invasive keratinizing squamous cell carcinoma (P < .001), and followed the morphologic distribution of atypical squamous epithelial cells. Overexpression of hTERT was comparable to that seen for p53 in invasive keratinizing squamous cell carcinoma (P  =  .62); significant differences were calculated for differentiated vulvar intraepithelial neoplasia (P  =  .003) and high-grade classic vulvar intraepithelial neoplasia (P  =  .001).
  
  
  CONCLUSIONS
  Human telomerase reverse transcriptase is upregulated in vulvar intraepithelial neoplasia and invasive keratinizing squamous cell carcinoma compared with nonneoplastic squamous epithelia of the vulva as an apparently early and preinvasive event in the neoplastic transformation, with development of cellular longevity and resistance to apoptosis by survivin activation as associated features, independent of the etiology of vulvar intraepithelial neoplasia.
authors.affiliation: Department of Obstetrics and Gynecology, Landesklinikum Thermenregion Baden, Moedling, Austria.
authors.forename: Alfred
authors.initials: A
authors.lastname: Wellenhofer
authors.forename: Hermann
authors.initials: H
authors.lastname: Brustmann
mesh_terms: D017209:Apoptosis; D002278:Carcinoma in Situ / Q000378:metabolism* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism*; D000077022:Survivin; D019098:Telomerase / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D007724:Vulvar Lichen Sclerosus / Q000378:metabolism / Q000473:pathology; D014846:Vulvar Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D000077022:Survivin; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C509186:TERT protein, human; D019098:Telomerase