PLoS ONE (Jan 2018)

P16INK4a expression in patients with penile cancer.

  • Vicenilma de Andrade Martins,
  • Jaqueline Diniz Pinho,
  • Antonio Augusto Lima Teixeira Júnior,
  • Leudivan Ribeiro Nogueira,
  • Fábio França Silva,
  • Victor Eduardo Maulen,
  • André Salim Khayat,
  • José de Ribamar Rodrigues Calixto,
  • Herikson Araújo Costa,
  • Leandra Naira Zambelli Ramalho,
  • Gyl Eanes Barros Silva

DOI
https://doi.org/10.1371/journal.pone.0205350
Journal volume & issue
Vol. 13, no. 10
p. e0205350

Abstract

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BACKGROUND:Infection with human papillomavirus (HPV) is reported to be present in 30-50% of penile cancer cases. The immunohistochemical test for p16INK4a is used as an indicator of the presence of HPV and as a prognostic marker for squamous cell carcinomas in various sites. However, the role of this marker in penile carcinoma has not yet been completely elucidated. The aim of this study was to analyze whether the expression of p16INK4a is associated with the presence of HPV, histological parameters, and survival in penile cancer. METHODS:A study was conducted from 2014 to 2016 that included 55 patients with penile carcinoma. HPV DNA was detected through PCR using fresh tumor tissue, and immunohistochemistry was performed for analysis of p16INK4a protein using paraffin-embedded tissue. Evaluation of histological parameters was performed following complete embedding of the tumor tissue in paraffin. RESULTS:HPV DNA (low-risk and high-risk genotypes) was found in 49 (89.1%) cases, and 46/49 (93.9%) showed high-oncogenic risk HPV (HR-HPV). Of the 22 cases positive for p16INK4a, HR-HPV DNA was present in 21 (95.5%) (p = 0.032). Regarding histological parameters, p16INK4a and HR-HPV were significantly associated only with tumor subtype (p = 0.036 and p = 0.032, respectively); all carcinomas with basaloid characteristics were positive for p16INK4a. Although HPV+ patients had a higher disease-free survival (p <0.001), p16INK4a expression was not associated with patient survival. CONCLUSIONS:Our study, using fresh tissue samples, showed the highest incidence of HPV compared to that observed in the literature. Expression of the p16INK4a protein was significantly associated with the presence of HR-HPV and this expression may serve as a marker for the presence of the virus. The p16INK4a protein was not associated with the histological prognostic parameters, with the exception of tumor subtype, nor with patient survival. In the results, we showed that the objective of the present study was reached.