Survivin as a marker of cervical intraepithelial neoplasia and high-risk human papillomavirus and a predictor of virus clearance and prognosis in cervical cancer

Margherita Branca, Colomba Giorgi, Donatella Santini, Luigi Di Bonito, Marco Ciotti, Silvano Costa, Arrigo Benedetto, Elena A. Casolati, Cartesio Favalli, Pierluigi Paba, Paola Di Bonito, Luciano Mariani, Stina Syrjänen, Donatella Bonifacio, Luisa Accardi, Francesca Zanconati, Kari Syrjänen

Research output: Contribution to journalArticlepeer-review

Abstract

We analyzed survivin as a marker of cervical intraepithelial neoplasia (CIN) and high-risk human papillomavirus (HR-HPV) and a predictor of HPV clearance and disease outcome in cervical cancer in 302 samples (squamous cell carcinomas [SCCs], 150; CIN lesions, 152) by immunohistochemical staining with survivin antibody and HPV testing using polymerase chain reaction. HR-HPV types were associated closely with CIN and SCC. There was a significant linear relationship between grade and intensity of survivin expression (P = .0001). Survivin overexpression also was associated strongly with HR-HPV type (P = .0001). Multivariate regression analysis revealed survivin and p16 INK4a as equally strong independent predictors of HR-HPV. Deregulated survivin expression did not predict clearance or persistence of HR-HPV after treatment of CIN or survival in cervical cancer in univariate (P = .417) or multivariate analysis. After adjustment for HR-HPV, stage, age, and tumor grade in the Cox regression model, only stage (P = .0001) and age (P = .0001) remained independent prognostic predictors. Survivin seems to be an early marker of cervical carcinogenesis. Up-regulated survivin expression was an independent predictor of HR-HPV in cervical lesions, most plausibly explained by its normal transcriptional repression by wild-type p53 being eliminated by HR-HPV E6 oncoprotein.

Original languageEnglish
Pages (from-to)113-121
Number of pages9
JournalAmerican Journal of Clinical Pathology
Volume124
Issue number1
DOIs
Publication statusPublished - Jul 2005

Keywords

  • Apoptosis inhibitor
  • Cervical cancer
  • Cervical intraepithelial neoplasia
  • CIN
  • High-risk HPV
  • Human papillomavirus
  • Prognosis
  • Survivin
  • Virus clearance

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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