mTOR Signaling Pathway in Penile Squamous Cell Carcinoma: Phosphorilated mTOR, Phosphorilated eIF4E and p53 Overexpression Correlates with Aggressive Tumors in a Mediterranean Population
Ines de Torres, Carla Ferrandiz-Pulido, Vicente Garcia-Patos, Emili Masferrer, Agusti Toll, Ramon M Pujol, Javier Hernandez-Losa, Santiago Ramon y Cajal. Hospital Universitari Vall d'Hebron, VHIR, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain; Hospital Universitari Vall d'Hebron, VHIR, UAB, Barcelona, Spain; Hospital del Mar, IMIM, UAB, Barcelona, Spain
Background: Squamous cell penile carcinoma (SCPC) is a rare neoplasm associated with a high risk of metastases and morbidity, being the presence of inguinal lymph node metastases the most important prognostic factor for survival. There is very limited data of the role of mTOR signaling pathway in SCPC carcinogenesis. Some molecular factors of this pathway could be predictive biomarkers and therapeutic targets for penile cancer.
Design: A cohort of 67 patients from two tertiary Hospitals with diagnosis of invasive SCPC between 1987 and 2010 were selected for the study with complete histological data and clinical follow-up.Tissue-microarrays blocks (Advanced Tissue Arrayer, Chemicon Int.) were constructed with the 67 cases of primary SCC and 8 cases with lymph node metastases. For each case, two selected cylinders of 2 mm from different and representative tumor areas were included. Normal tissue from the same specimen was used as control in all cases. Inmunohistochemical staining was performed for p-mTOR,p-MAPK,p-4EBP1,eIF4E and p-eIF4E (Ventana Medical Systems, Inc) The expression was evaluated using a semiquantitative method scored on a scale from 0 to 300 (HScore). The results were analyzed by means the SPSS Data Analysis Program 18.0.
Results: p-mTOR protein was strongly expressed in 37 (58%) SCPC and correlated with tumor stage and metastases (p: 0.043). 13.6% of SCPC showed p53 expression mostly in high stage tumors (p=0.009) and metastases development (p=0.004). Most invasive SCPC expressed p4EBP1 (84%) and correlated with its expression in the lymph node metastases (p=0.03) and with pMAPK expression (p=0.007). 41% of invasive SCPC showed strong nuclear p-eIEF4 expression and associated with a higher risk of metastatic disease (p=0.004). Finally p-mTOR, p53 and p-eIF4E overexpression were associated with poor outcome (mortality and /or node metastases) and showed independent prognostic significance (p<0.005).
Conclusions: p-mTOR pathway activation may contributed to tumor progression and poor outcome in SCPC. The role of mTOR inhibitors as well as chemical compounds that prevent the phosphorilation of eIF4E could be a future targeting treatment.
Category: Genitourinary (including renal tumors)
Tuesday, March 5, 2013 1:00 PM
Poster Session IV # 215, Tuesday Afternoon