Epithelial-mesenchymal transition (EMT) phenotype at invasion front of squamous cell carcinoma of the penis influences oncological outcomes

• Published in: Urologic oncology 2016-10, Vol.34 (10), p.433.e19-433.e26
• Main Authors: da Cunha, Isabela Werneck, M.D., Ph.D, Souza, Maria José L., M.D, da Costa, Walter Henriques, M.D., Ph.D, Amâncio, Alice M., Ph.D, Fonseca, Francisco Paulo, Ph.D, Zequi, Stenio de Cassio, M.D., Ph.D, Lopes, Ademar, M.D., Ph.D, Guimarães, Gustavo Cardoso, M.D., Ph.D, Soares, Fernando, M.D., Ph.D
• Format: Article
• Language: English
• Subjects: Adult; Aged; Biomarkers, Tumor - metabolism; Cadherins - metabolism; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - secondary; Case-Control Studies; Epithelial-Mesenchymal Transition; Humans; Kaplan-Meier Estimate; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Grading; Neoplasm Invasiveness; Penile cancer; Penile carcinoma; Penile Neoplasms - metabolism; Penile Neoplasms - pathology; Penis - metabolism; Phenotype; Prognosis; Prognostic markers; Proportional Hazards Models; Retrospective Studies; Survival Rate; Urology; Vimentin - metabolism
• ISSN: 1078-1439; 1873-2496
• DOI: 10.1016/j.urolonc.2016.05.015

Abstract Objective Our aims were to evaluate epithelial-mesenchymal transition (EMT) as a useful prognostic marker in penile carcinoma (PC), and establish an objective criterion to define EMT in PC specimens. Materials and Methods A total of 149 consecutive cases surgically treated for PC were retrospectively selected. E-cadherin (E-CAD) and vimentin immunohistochemical expressions were evaluated. A combined analysis was performed using both markers to determine EMT status. To establish a normal control to E-CAD expression, we included 14 cases from circumcisions from patients without any neoplastic disease and 77 cases of tumor-free margins. The analyses of tumor samples were evaluated in 2 different areas of the tumor. The first one was in the tumor core. The second analyses were performed on the deepest infiltrative edge of the tumor, nominated invasion front. Cases were classified into EMT absent group, partial EMT group and complete EMT group. Overall survival (OS) and cancer-specific survival (CSS) were analyzed. Kaplan-Meier curves and the log-rank test were used. Cox proportional hazards model was used to determine which variables influenced survival. Results Tumor specimens presented a significant loss of expression of E-CAD when compared with normal epithelium. Vimentin expression in more than 10% of tumor cells was observed in 50 cases. EMT status was associated with histologic grade, pattern of invasion, lymph node metastasis, and perineural and vascular invasion. Further, 10-year OS and CSS rates in patients with presence and absence of complete EMT status were 38.0% and 55.6%; and 48.0% and 91.9%, respectively. EMT status significantly affected CSS and OS rates even after patients were grouped based on lymph node involvement status. The presence of complete EMT status was associated with both CSS and OS rates. Patients in the complete EMT group had a higher risk of death from cancer (hazard ratio = 7.6, P