RESUMO
BACKGROUND: Penile cancer is high in some underdeveloped countries. Signal transducer and activator of transcription 3 (STAT3) and CD44, CD24, and SOX2+ are known to be markers of diagnosis and prognosis in other cancers, but without studies in penile cancer. METHODS: A cross-sectional study was conducted at the Hospital de Cancer de Pernambuco from March 2015 to December 2017. We performed SOX2, STAT3, CD24, and CD44 analyses in blood and tumor tissue by flow cytometry. RESULTS: High levels of CD44highCD24low, CD44highCD24lowpSTAT3+ and CD44hig hCD24low in the blood of patients compared to the controls (p < 0.05). Low of SOX2+ T cells in blood of patients compared to controls. High CD44highCD24low levels in patients with perineural invasion (PNI), tumor size > 3 cm, and pT2 stage (p < 0.05). High T cell levels in the blood and tumor tissue of patients with tumor ≤3 cm (p < 0.05). Increased SOX2+ T cells in blood of patients with PNI (-) and pT1 stage (p < 0.05). CD44highCD24lowpSTAT3+ (r = 0.669; p = 0.024) and SOX2+T cells (r = 0.404, p = 0.029) correlation were observed between blood and tumor tissue in penile cancer patients. CONCLUSION: CD44, CD24, and SOX2 molecules were markers of advanced disease associated with the worst prognosis in CaPe. However, pSTAT3 and T cells were associated with a more favorable prognosis in this study.
RESUMO
PURPOSE: Penile cancer has a high incidence in developing countries. The standard treatment is removal of the primary tumor and, when necessary, inguinal lymphadenectomy. Currently, the most important prognostic factor is lymph node disease, however, the available staging methods are inaccurate, and the high morbidity rate of lymphadenectomy has stimulated the study of predictive biomarkers of lymph node metastasis for selecting the patients who need lymphadenectomy. SOX2, STAT3 and CD44high/CD24low were chosen because they have provided good predictive results in other squamous cell carcinoma (SCC), although there are no studies for penile cancer. Thus, the expression of SOX2, STAT3, CD24+, and CD44+ in the penile cancer tumor microenvironment was investigated for correlation with tumor behavior in SCC. METHODS: This observational, prospective, translational study included 34 men and investigated the expression of SOX2, STAT3, CD24+, and CD44+ in tumor tissue by flow cytometry. RESULTS: The median age of the 38 evaluated patients with penile cancer was 61 (37-80) years. Most patients presented a tumor located on the glans penis (82.3%), with the usual histological type (79.4%) and 61.7% of patients presented stage pT2. No metastasis was found in 85.3% of patients. The expression of SOX2, STAT3 and CD44high/CD24low in the microenvironment of penile SCC treated with lymphadenectomy was significantly associated with aggressive tumor behavior (p < 0.05). STAT3 expression shows discrepant points when evaluated in context of angiolymphatic vascular invasion. CONCLUSION: SOX2, STAT3 and CD44high/CD24low in penile SCC can be indicators of prognosis, allowing for selection of more aggressive treatment when necessary.