title: Pathologic and imunohistochemical characterization of tumoral inflammatory cell infiltrate in invasive penile squamous cell carcinomas: Fox-P3 expression is an independent predictor of recurrence.
abstract: 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.
authors.affiliation: Department of Anatomic Pathology, A. C. Camargo Cancer Center, Fundação Antonio Prudente, São Paulo, Brazil, vassallomeister@gmail.com.
authors.forename: José
authors.initials: J
authors.lastname: Vassallo
authors.forename: André Fellipe Freitas
authors.initials: AF
authors.lastname: Rodrigues
authors.forename: Antonio Hugo J F M
authors.initials: AH
authors.lastname: Campos
authors.forename: Rafael Malagoli
authors.initials: RM
authors.lastname: Rocha
authors.forename: Isabela Werneck
authors.initials: IW
authors.lastname: da Cunha
authors.forename: Stênio Cássio
authors.initials: SC
authors.lastname: Zequi
authors.forename: Gustavo Cardoso
authors.initials: GC
authors.lastname: Guimarães
authors.forename: Francisco Paulo
authors.initials: FP
authors.lastname: da Fonseca
authors.forename: Ademar
authors.initials: A
authors.lastname: Lopes
authors.forename: Antonio
authors.initials: A
authors.lastname: Cubilla
authors.forename: Fernando Augusto
authors.initials: FA
authors.lastname: Soares
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology / Q000821:virology; D051858:Forkhead Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000473:pathology; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000473:pathology / Q000821:virology; D009367:Neoplasm Staging; D027383:Papillomaviridae / Q000472:pathogenicity; D010412:Penile Neoplasms / Q000235:genetics* / Q000473:pathology; D011379:Prognosis
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors