Transição epitélio-mesenquimal em portadores de câncer de pênis sem metástases linfonodais / Epithelium-mesenchymal transition in penile cancer patients without lymph node metastases

Introdução: O carcinoma escamoso do pênis é uma neoplasia rara, mas sua incidência e mortalidade específica vêm aumentando. No Brasil, o câncer de pênis constitui 2,1% das neoplasias em homens. O acometimento dos linfonodos inguinais é o fator prognóstico mais importante. Comparados aos pacientes com linfonodos positivos, aqueles com linfonodos histologicamente negativos (pN0) têm o melhor prognóstico; entretanto, a ausência de metástases linfonodais não garante a cura, haja vista que uma proporção destes apresenta recorrência locorregional ou progressão tumoral após o tratamento. Poucos estudos examinaram populações de pacientes com pN0 ou clinicamente negativos (cN0). Objetivos: Avaliar o impacto da expressão imuno-histoquímica da E-caderina e da vimentina como fatores prognósticos para sobrevida global, sobrevida câncer específica e sobrevida livre de doença em pacientes com carcinoma escamoso do pênis clinicamente ou histologicamente negativos para metástase linfonodal. Material e Métodos: Coorte retrospectiva de 116 pacientes cN0 e pN0 com carcinoma escamoso do pênis consecutivamente tratados no A.C.Camargo Cancer Center entre 1953-2017. As variáveis registradas incluíram idade, estadiamento TNM, subtipo histológico, grau de diferenciação tumoral, invasão vascular microscópica, invasão perineural, padrão microscópico da fronte de invasão tumoral (expansivo/infiltrativo) e expressão imuno-histoquímica das proteínas E-caderina e vimentina. As amostras de tumor foram analisadas no centro do tumor e na fronte de invasão tumoral. As análises de sobrevida foram realizadas usando curvas de Kaplan-Meier e testes de log-rank. O modelo de riscos proporcionais de Cox foi usado para determinar quais variáveis influenciaram as taxas de sobrevida global, câncer específica e livre de doença. Resultados: O tempo de seguimento médio foi de 176 meses. A presença de invasão perineural foi associada à alta expressão de vimentina no centro tumoral (p = 0,013), à perda da expressão de Ecaderina no centro do tumor (p = 0,026) e na fronte de invasão tumoral (p = 0,02). A perda da expressão imuno-histoquímica da E-caderina na fronte de invasão e a presença de invasão perineural foram independentemente associadas à sobrevida livre de doença. Conclusões: A perda da expressão imuno-histoquímica da E-caderina na fronte de invasão tumoral e a presença de invasão perineural no tumor primário foram associadas a uma menor sobrevida livre de doença. Alta expressão de vimentina no centro do tumor, perda da expressão da Ecaderina no centro do tumor e na fronte de invasão do tumor foram associadas à presença de invasão perineural no tumor primário.

Introduction: Penile squamous cell carcinoma is a rare neoplasm, but its incidence and specific mortality have been increasing. In Brazil, penile squamous cell carcinoma constitutes 2.1% of neoplasms in men. The involvement of inguinal lymph nodes is the most important prognostic factor. Compared to patients with positive lymph nodes, histologically negative patients (pN0) have the best prognosis; however, the absence of lymph node metastases does not guarantee a cure. Some pN0 patients exhibit locoregional recurrence or tumor progression after treatment. Few studies have examined patient populations with histologically negative (pN0) or clinically negative (cN0) lymph nodes. Objectives: To evaluate the impact of E-cadherin and vimentin expression as prognostic factors for overall survival, cancer-specific survival, and disease-free survival in patients with penile squamous cell carcinoma who were clinically or histologically negative for lymph node metastasis. Material and Methods: Retrospective cohort of 116 patients (cN0 and pN0) treated at A. C. Camargo Cancer Center from 1953 to 2017. Recorded variables included age, TNM staging, histological subtype, degree of tumor differentiation, microscopic vascular invasion, perineural invasion, microscopic pattern of the tumor invasion front (pushing/infiltrating) and vimentin and E-cadherin immunohistochemical expression. Tumor samples were analyzed at the tumor center and at the tumor invasion front. Survival analyses were performed using Kaplan-Meier curves and log-rank testing. Cox's proportional hazards model was used to determine which variables influenced overall survival, disease-free survival, or cancer specific survival. Results: The median follow-up time was 176 months. Perineural invasion was associated with high vimentin expression at tumor center (p = 0.013), loss of E-cadherin expression in the tumor center (p = 0.026) and at the front invasion (p = 0.02). Loss of immunohistochemical E-cadherin expression at the front invasion and the presence of perineural were independently associated with disease-free survival. Conclusions: Lower disease-free survival was associated with loss of immunohistochemical E-cadherin expression at the tumor invasion front, and the presence of perineural invasion. High vimentin expression in the tumor center, loss of E-cadherin expression in the tumor center and in the tumor invasion front were associated with the presence of perineural invasion in the primary tumor.

Tumor histologic grade is the most important prognostic factor in patients with penile cancer and clinically negative lymph nodes not submitted to regional lymphadenectomy

ABSTRACT Introduction: The presence and extension of inguinal lymph node metastasis are the main prognostic factors in patients with penile cancer. Physical exam and image exams are not adequate to evaluate inguinal lymph nodes and many patients are submitted to non-therapeutic lymphadenectomies. However, it is known that not all patients with clinically or histologically negative inguinal lymph nodes evolve favorably. Casuistic and Methods: the authors evaluated the clinical and pathologic characteristics of 163 patients with penile carcinoma and clinically negative inguinal lymph nodes followed for three or more years and their impact on global survival (GS) and cancer-specific survival (CSS) in the 10-year follow-up. Primary pathologic tumor stage (p=0.025) and the presence of high grade of tumor differentiation (p=0.018) were predictive of CSS. The presence of high grade tumor was an independent specific prognostic factor of death risk (RR 14.08; p=0.019). Conclusion: high histologic grade was an independent predictive factor of specific death risk in patients with penile carcinoma and clinically negative lymph nodes followed for three or more years.

Tumor histologic grade is the most important prognostic factor in patients with penile cancer and clinically negative lymph nodes not submitted to regional lymphadenectomy.

INTRODUCTION: The presence and extension of inguinal lymph node metastasis are the main prognostic factors in patients with penile cancer. Physical exam and image exams are not adequate to evaluate inguinal lymph nodes and many patients are submitted to non-therapeutic lymphadenectomies. However, it is known that not all patients with clinically or histologically negative inguinal lymph nodes evolve favorably. CASUISTIC AND METHODS: the authors evaluated the clinical and pathologic characteristics of 163 patients with penile carcinoma and clinically negative inguinal lymph nodes followed for three or more years and their impact on global survival (GS) and cancer-specific survival (CSS) in the 10-year follow-up. Primary pathologic tumor stage (p=0.025) and the presence of high grade of tumor differentiation (p=0.018) were predictive of CSS. The presence of high grade tumor was an independent specific prognostic factor of death risk (RR 14.08; p=0.019). CONCLUSION: high histologic grade was an independent predictive factor of specific death risk in patients with penile carcinoma and clinically negative lymph nodes followed for three or more years.

Características clinicopatológicas e fatores prognósticos em portadores decâncer de pênis com linfonodos negativos submetidos ou não a linfadenectomia inguinal / Clinicopathological characteristics and prognostic factors in patientswith penile cancer with negative lymph nodes undergoing or not to inguinallymphadenectomy

Introdução: A presença e a extensão de metástases em linfonodos inguinaisrepresentam o principal fator prognóstico em pacientes com carcinoma peniano. Oexame físico e os métodos de imagem são inacurados para a avaliação dos linfonodos inguinais e muitos pacientes são submetidos a linfadenectomias nãoterapêuticas. Em virtude desta imprecisão e das complicações associadas às dissecções ilioinguinais são apresentadas propostas de linfadenectomias odificadas,com redução dos limites de dissecção e consequentemente do número de linfonodos. Entretanto, poucos são os estudos na literatura a respeito dos pacientes com linfonodos histologicamente negativos ou clinicamente negativos que não sãosubmetidos a essa dissecção. Casuística e Métodos: Neste estudo os autoresavaliaram as características clinicopatológicas e epidemiológicas de 261 pacientes com carcinoma peniano e linfonodos histologicamente negativos (pN0, 96 pacientes) ou clinicamente negativos por período igual ou superior a 3 anos (cN0, 165 pacientes) e seus respectivos impactos prognósticos na sobrevida global (SG), sobrevida câncer específica (SCE) e sobrevida livre de doença (SLD) em 10 anos. Investigou-se a existência de subgrupos de evolução clínica distinta. Avaliou-se o número de linfonodos dissecados e pesquisou-se valores de corte que pudessem discriminar desfechos clínicos de importância. A idade maior que 60 anos (p<0,001), o estádio clínico do tumor primário (p=0,005), a invasão uretral (p=0,045) e a presença de alto grau de diferenciação tumoral (p=0,024) foram preditores de SG nos pacientes com linfonodos clinicamente negativos. Neste mesmo subgrupo, a presença de tumor de alto grau foi fator prognóstico independente de risco de óbito específico (RR 2,05; IC 95%[1,37-3,01]) e de recidiva neoplásica (RR1,44; IC 95%[1,12-1,73]). Para os pacientes pN0, a idade maior que 60 anos (p=0,026), a nãocircuncisão prévia ao diagnóstico do câncer de pênis (p=0,03), o estádio clínico (p<0,001)...

Introduction: The presence and extension of metastasis to inguinal lymph nodesrepresent the main prognostic factor in patients with penile carcinoma. Physicalexamination and available imaging methods for the assessment of regional lymph nodes are not reliable and many patients undergo to unnecessary surgery. Due to this imprecision and the complications associated with ilioinguinal dissections some modified lymphadenectomy have been proposed, reducing the limit of dissection andconsequently reducing the number of lymph nodes. However, there are few studies in the literature regarding patients with histologically negative or clinically negative lymph nodes that are not subject to this dissection. Material and methods: in this study the authors evaluated the clinicopathologic and epidemiological features of 261 patients with penile carcinoma and lymph nodes histologically negative (pN0, 96 patients) or clinically negative nodes who were followed for 3 or more years with no recurrence (cN0, 261 patients) and their respective prognostic impact on 10-year overall survival (OS), cancer-specific survival (CSS) and disease-free survival (DFS). The existence of distinct clinical evolution subgroups was investigated. We evaluated the number of dissected lymph nodes andwe look for cut-off values thatcould discriminate important clinical outcomes. Age greater than 60 years (p <0.001), the clinical stage of primary tumor (p=0.005), urethral invasion (p = 0.045) and the presence of high-grade tumor differenciation (p=0.024) were predictors of OS in patients with clinically negative lymph nodes. In this subgroup, the presence of high grade tumor was independent prognostic factor of specific death risk (RR 2.05; IC 95% [1.37 - 3.01]) and cancer recurrence (RR 1.44; IC 95% [1.73 - 1.12]). For patients pN0, age greater than 60 years (p=0.026), the absent of circumcision previously to the diagnosis of penile cancer (p=0.03), the clinical stage (p<0.001)...

Características clinicopatológicas e fatores prognósticos em portadores de câncer de pênis com linfonodos negativos submetidos ou não a linfadenectomia inguinal / Clinicopathological characteristics and prognostic factors in patients with penile cancer with negative lymph nodes undergoing or not to inguinal lymphadenectomy

Introdução: A presença e a extensão de metástases em linfonodos inguinais representam o principal fator prognóstico em pacientes com carcinoma peniano. O exame físico e os métodos de imagem são inacurados para a avaliação dos linfonodos inguinais e muitos pacientes são submetidos a linfadenectomias não terapêuticas. Em virtude desta imprecisão e das complicações associadas às dissecções ilioinguinais são apresentadas propostas de linfadenectomias modificadas, com redução dos limites de dissecção e consequentemente do número de linfonodos. Entretanto, poucos são os estudos na literatura a respeito dos pacientes com linfonodos histologicamente negativos ou clinicamente negativos que não são submetidos a essa dissecção. Casuística e Métodos: Neste estudo os autores avaliaram as características clinicopatológicas e epidemiológicas de 261 pacientes com carcinoma peniano e linfonodos histologicamente negativos (pN0, 96 pacientes) ou clinicamente negativos por período igual ou superior a 3 anos (cN0, 165 pacientes) e seus respectivos impactos prognósticos na sobrevida global (SG), sobrevida câncer específica (SCE) e sobrevida livre de doença (SLD) em 10 anos. Investigou-se a existência de subgrupos de evolução clínica distinta. Avaliou-se o número de linfonodos dissecados e pesquisou-se valores de corte que pudessem discriminar desfechos clínicos de importância. A idade maior que 60 anos (p<0,001), o estádio clínico do tumor primário (p=0,005), a invasão uretral (p=0,045) e a presença de alto grau de diferenciação tumoral (p=0,024) foram preditores de SG nos pacientes com linfonodos clinicamente negativos. Neste mesmo subgrupo, a presença de tumor de alto grau foi fator prognóstico independente de risco de óbito específico (RR 2,05; IC 95%[1,37-3,01]) e de recidiva neoplásica (RR1,44; IC 95%[1,12-1,73]). Para os pacientes pN0, a idade maior que 60 anos (p=0,026), a não circuncisão prévia ao diagnóstico do câncer de pênis (p=0,03), o estádio clínico (p<0,001) e patológico (p=0,014) do tumor primário e a invasão uretral (p=0,046) influenciaram a SG. O critério patológico fronte de invasão tipo "infiltrating" foi associado a menor SCE (p=0,027) e a menor SLD (p=0,019). Conclusão: O alto grau histológico foi fator preditor independente de risco de óbito ou de recidiva neoplásica no grupo cN0 e a fronte de invasão tipo "infiltrating" foi associada a menor probabilidade de SCE e SLD no grupo pN0.

Introduction: The presence and extension of metastasis to inguinal lymph nodes represent the main prognostic factor in patients with penile carcinoma. Physical examination and available imaging methods for the assessment of regional lymph nodes are not reliable and many patients undergo to unnecessary surgery. Due to this imprecision and the complications associated with ilioinguinal dissections some modified lymphadenectomy have been proposed, reducing the limit of dissection and consequently reducing the number of lymph nodes. However, there are few studies in the literature regarding patients with histologically negative or clinically negative lymph nodes that are not subject to this dissection. Material and methods: in this study the authors evaluated the clinicopathologic and epidemiological features of 261 patients with penile carcinoma and lymph nodes histologically negative (pN0, 96 patients) or clinically negative nodes who were followed for 3 or more years with no recurrence (cN0, 261 patients) and their respective prognostic impact on 10-year overall survival (OS), cancer-specific survival (CSS) and disease-free survival (DFS). The existence of distinct clinical evolution subgroups was investigated. We evaluated the number of dissected lymph nodes andwe look for cut-off values that could discriminate important clinical outcomes. Age greater than 60 years (p < 0.001), the clinical stage of primary tumor (p=0.005), urethral invasion (p = 0.045) and the presence of high-grade tumor differenciation (p=0.024) were predictors of OS in patients with clinically negative lymph nodes. In this subgroup, the presence of high grade tumor was independent prognostic factor of specific death risk (RR 2.05; IC 95% [1.37 - 3.01]) and cancer recurrence (RR 1.44; IC 95% [1.73 - 1.12]). For patients pN0, age greater than 60 years (p=0.026), the absent of circumcision previously to the diagnosis of penile cancer (p=0.03), the clinical stage (p<0.001) and pathological (p=0.014) of the primary tumor and the urethral invasion (p=0.046) influenced the OS. The pathological criteria front invasion "infiltrating" was associated with a lower CSS (p=0.027) and the lowest DFS (p=0.019). Conclusions: The high histologic grade was an independent predictor of risk of death or neoplastic recurrence in cN0 group and the front invasion "infiltrating" was associated with a lower probability of CSS and DFS in pN0 group.

Sex with animals (SWA): behavioral characteristics and possible association with penile cancer. A multicenter study.

INTRODUCTION: Zoophilia has been known for a long time but, underreported in the medical literature, is likely a risk factor for human urological diseases. AIM: To investigate the behavioral characteristics of sex with animals (SWA) and its associations with penile cancer (PC) in a case-control study. METHODS: A questionnaire about personal and sexual habits was completed in interviews of 118 PC patients and 374 controls (healthy men) recruited between 2009 and 2010 from 16 urology and oncology centers. MAIN OUTCOME MEASURES: SWA rates, geographic distribution, duration, frequency, animals involved, and behavioral habits were investigated and used to estimate the odds of SWA as a PC risk factor. RESULTS: SWA was reported by 171 (34.8%) subjects, 44.9% of PC patients and 31.6% of controls (P < 0.008). The mean ages at first and last SWA episode were 13.5 years (standard deviation [SD] 4.4 years) and 17.1 years (SD 5.3 years), respectively. Subjects who reported SWA also reported more venereal diseases (P < 0.001) and sex with prostitutes (P < 0.001), and were more likely to have had more than 10 lifetime sexual partners (P < 0.001) than those who did not report SWA. SWA with a group of men was reported by 29.8% of subjects and SWA alone was reported by 70.2%. Several animals were used by 62% of subjects, and 38% always used the same animal. The frequency of SWA included single (14%), weekly or more (39.5%), and monthly episodes (15%). Univariate analysis identified phimosis, penile premalignancies, smoking, nonwhite race, sex with prostitutes, and SWA as PC risk factors. Phimosis, premalignant lesions, smoking, and SWA remained as risk factors in multivariate analysis. However, SWA did not impact the clinicopathological outcomes of PC. CONCLUSION: SWA is a risk factor for PC and may be associated with venereal diseases. New studies are required in other populations to test other possible nosological links with SWA.