MP37-15 PI3K-AKT-MTOR PATHWAY IN PENILE SQUAMOUS CELL CARCINOMA: CLINICAL SIGNIFICANCE OF PTEN, AKT AND S6 EXPRESSION

You have accessJournal of UrologySexual Function/Dysfunction: Penis/Testis/Urethra: Benign Disease & Malignant Disease I1 Apr 2018MP37-15 PI3K-AKT-MTOR PATHWAY IN PENILE SQUAMOUS CELL CARCINOMA: CLINICAL SIGNIFICANCE OF PTEN, AKT AND S6 EXPRESSION Mounsif Azizi, Dominic H. Tang, Daniel Verduzco, Juan Chipollini, Charles C. Peyton, Jun-Min Zhou, Braydon Schaible, Jasreman Dhillon, and Philippe E. Spiess Mounsif AziziMounsif Azizi More articles by this author , Dominic H. TangDominic H. Tang More articles by this author , Daniel VerduzcoDaniel Verduzco More articles by this author , Juan ChipolliniJuan Chipollini More articles by this author , Charles C. PeytonCharles C. Peyton More articles by this author , Jun-Min ZhouJun-Min Zhou More articles by this author , Braydon SchaibleBraydon Schaible More articles by this author , Jasreman DhillonJasreman Dhillon More articles by this author , and Philippe E. SpiessPhilippe E. Spiess More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.1221AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The PI3K-AKT-mTOR signaling pathway is commonly found to be activated in certain malignancies. Only few studies have examined the role of biomarkers in this signaling pathway in penile carcinoma squamous cell carcinoma (pSCC). We sought to determine the clinical significance of PTEN, AKT, and S6 expression and its potential use in predicting outcomes in men with pSCC. METHODS Tissue microarrays were constructed for 57 consecutive cases of invasive pSCC with known HPV status treated at our institution between 1999 and 2013. Immunohistochemistry was performed to stain for PTEN, AKT, and S6. Expression was evaluated using a semi-quantitative H-score on a scale of 0 to 300. Recurrence-free survival (RFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Cox regression proportional hazard model was used to identify predictors of survival and recurrence. RESULTS Median age was 60 years and median follow-up was 25 months. 28% (n=16) of patients had high-grade (G3/G4) tumors. 24 patients (42.1%) had locally advanced disease (pT3-4) and 31 patients (54.4%) had lymph node involvement (pN1-3). 32 patients (56.1%) had positive lymphovascular invasion (LVI). HPV ISH was positive in 23 patients (40.4%). PTEN, AKT, and S6 were overexpressed in 14 (25%), 27 (47%), and 12 (21%) patients, respectively. On adjusted analysis, low expression of S6 was an independent predictor of poorer OS (OS) (HR= 6.15, 1.55-24.36) while low expression of AKT was an independent predictor of poorer RFS (HR= 3.95, 1.47-10.59). On Kaplan Meier analysis, AKT and S6 overexpression were associated with improved OS (p=0.011 and p=0.039, respectively) (figure a) and RFS (p=0.004 and p=0.015, respectively)(figure b). CONCLUSIONS AKT and S6 overexpression were associated with improved overall and recurrence-free survival in invasive pSCC patients. Expression of biomarkers in the PI3K-AKT-mTOR signaling pathway may be used as a prognostic predictor in penile cancer. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e497 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Mounsif Azizi More articles by this author Dominic H. Tang More articles by this author Daniel Verduzco More articles by this author Juan Chipollini More articles by this author Charles C. Peyton More articles by this author Jun-Min Zhou More articles by this author Braydon Schaible More articles by this author Jasreman Dhillon More articles by this author Philippe E. Spiess More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...