Tumor Biology

, Volume 36, Issue 4, pp 2509–2516 | Cite as

Pathologic and imunohistochemical characterization of tumoral inflammatory cell infiltrate in invasive penile squamous cell carcinomas: Fox-P3 expression is an independent predictor of recurrence

  • José Vassallo
  • André Fellipe Freitas Rodrigues
  • Antonio Hugo J. F. M. Campos
  • Rafael Malagoli Rocha
  • Isabela Werneck da Cunha
  • Stênio Cássio Zequi
  • Gustavo Cardoso Guimarães
  • Francisco Paulo da Fonseca
  • Ademar Lopes
  • Antonio Cubilla
  • Fernando Augusto Soares
Research Article


Penile carcinomas (PeCa) are relatively rare, but devastating neoplasms, more frequent among people of underprivileged socioeconomic status. There is mounting evidence that immune cells may trigger various mechanisms that enhance tumor growth and metastasis, but no data on the peritumoral inflammation is available for PeCa. The objectives of the present study are to evaluate the immunohistomorphology of tumoral inflammation in PeCa, and to correlate it with clinicopathological parameters, which could contribute to the prognostic evaluation. One hundred and twenty-two patients with the diagnosis of usual-type squamous cell penile carcinoma were included. Paraffin-embedded tissue was submitted to immunohistochemical evaluation of p16 protein, CD3, CD4, CD8, CD20, CD68, CD138, granzyme B, and Fox-P3. The Fisher’s exact test was employed for comparison between histological variables and parameters, and the Kaplan-Meier method for the analysis of survival. Improved 5-year overall survival was significantly associated to age ≤60 years, stage I + II, tumor size T1 + T2, lymph node status N0, and absent perineural invasion. In a multivariate analysis age ≥60 years, presence of lymph node metastasis, urethral invasion, and high histologic grade retained a significantly more unfavorable outcome. Improved 5-year failure free survival was associated to stage of the disease I + II, lymph node status N0, absence of perineural, vascular, and urethral invasion, and Fox-P3 expression. In a multivariate analysis, presence of lymph node metastasis, perineural and vascular invasion, and of Fox-P3-positive lymphocytes together with low inflammatory infiltrate retained a significantly more unfavorable outcome. These results support the prognostic value of determining the levels of Fox-P3-positive lymphocytes by immunohistochemistry in PeCa, as this parameter adds value to the traditional clinicopathological features.


Penile carcinoma Human papillomavirus Tumor immunology Fox-P3-positive lymphocytes 



Support was received from Fapesp (Fundação de Amparo à Pesquisa do Estado de São Paulo), CAPES (Coordenação de Aperfeiçoamento do Pessoal de Nível Superior), and CNPq (National Counsel of Technological and Scientific Development), Brazil. The authors acknowledge Dr. Lara Termini and Dr. Luiza L. Villa for support with genotyping of HPV.

Conflicts of interest

The authors disclaim any potential conflict of interests.


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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • José Vassallo
    • 1
    • 2
  • André Fellipe Freitas Rodrigues
    • 1
  • Antonio Hugo J. F. M. Campos
    • 1
  • Rafael Malagoli Rocha
    • 1
  • Isabela Werneck da Cunha
    • 1
  • Stênio Cássio Zequi
    • 3
  • Gustavo Cardoso Guimarães
    • 1
  • Francisco Paulo da Fonseca
    • 3
  • Ademar Lopes
    • 3
  • Antonio Cubilla
    • 4
  • Fernando Augusto Soares
    • 1
  1. 1.Department of Anatomic PathologyA. C. Camargo Cancer CenterSão PauloBrazil
  2. 2.Laboratory of Molecular and Investigative Pathology, CIPEDState University of Campinas Medical School (Unicamp)CampinasBrazil
  3. 3.Urology Division of the Department of Pelvic Surgical OncologyA. C. Camargo Cancer CenterSão PauloBrazil
  4. 4.Instituto de Patología e Investigación and Universidad Nacional de AsuncionAsunciónParaguay

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