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Expression of p16INK4a and cervical infection with high-risk human papillomavirus are not related to p53 activity in cervical intraepithelial neoplasia
  1. J. F. Bragança*,
  2. L. O. Sarian*,
  3. D. R. Pitta*,
  4. A. B. Maito*,
  5. J. Vassallo,
  6. F. Pignataro,
  7. L. A. Andrade and
  8. S. Derchain*
  1. * Departments of Obstetrics and Gynecology and
  2. Department of Pathology, Universidade Estadual de Campinas (Unicamp), Campinas, Brazil
  1. Address correspondence and reprint requests to: Sophie Derchain, MD, PhD, Rua Antônio Hossri, 629, Cidade Universitária, 13083-370, Campinas, SP, Brazil. Email: derchain{at}


The objective of the study was to investigate the expression of p53 and p16INK4a in cervical intraepithelial neoplasia (CIN) and their relation with disease severity and high-risk human papillomavirus (HR-HPV) status. A series of 125 women with previous positive Pap smear were selected for this cross-sectional study. All patients underwent gynecological examination, including colposcopy. Specimens for Pap smears, Hybrid Capture 2 (HC2) test, and pathologic analysis were obtained. After evaluation of CIN grade, immunohistochemical detection of proteins p53 and p16INK4a was performed on paraffin-embedded sections. The extent of immunoexpression of both proteins was analyzed in relation to CIN grade and HR-HPV status. CIN was graded as 1 in 21, 2 in 17, and 3 in 87 specimens. p16INK4a positivity (at least 5% of epithelial cells stained) was found in 99 of 125 cases (79.2%) and was significantly higher in high-grade lesions as compared to low-grade CIN (P< 0.001). The expression of p53 did not differ across histologic strata. Protein expression neither of p16INK4a nor of p53 correlated with HR-HPV status. Expression of p16INK4a was not related with that of p53. Our study gives further support to previous findings of strong association of p16INK4a immunostaining with severity of epithelial atypia, but this protein may not be considered a predictor of HR-HPV status determined with HC2. By contrast, immunoexpression of p53 was related neither to CIN grade nor to HR-HPV status.

  • cancer
  • cervical intraepithelial neoplasia
  • immunohistochemistry
  • tumor marker

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