Evaluation of the Prognostic Role of pSTAT3 Expression in Temporal Bone Squamous Cell Carcinoma *Gino Marioni, †Raoul Nucci, ‡Filippo Marino, ‡Rocco Cappellesso, §Marta Pillon, kElisabetta Zanoletti, ‡Luciano Giacomelli, *Sebastiano Franchella, ¶Paola Billo, †Roberto Pareschi, and kAlessandro Martini *Department of Neurosciences, Otolaryngology Section, Padova University Hospital, Padova; ÞOtorhinolaryngology Division, Legnano Hospital, Legnano; þDepartment of Medicine DIMED, §Pediatric Onco-Hematology Unit, and kDepartment of Neurosciences, Otosurgery Unit, Padova University Hospital, Padova; and ¶Anatomic Pathology Division, Legnano Hospital, Legnano, Italy Objective: Temporal bone squamous cell carcinoma (SCC) accounts for less than 0.2% of all head and neck tumors. Although some progress has been made in treating this ag- gressive tumor, the prognosis in advanced cases remains poor. More effective therapeutic strategies need to be consid- ered, including receptor-mediated carcinoma-targeted therapy. Phosphorylated STAT3 (pSTAT3) regulates many genes that are necessarily expressed in cancer initiation, development, and progression, being involved in proliferation, anti- apoptosis, invasion, angiogenesis, and immune surveillance evasion. The aim of the present study was to preliminarily investigate the potential prognostic role of pSTAT3 expression in temporal bone SCC. Study Design: Retrospective clinicopathologic investigation. Setting: Tertiary referral centers. Patients: Twenty-five consecutively operated patients with primary temporal bone SCC. Intervention: pSTAT3 immunohistochemical expression in primary temporal bone SCCs was assessed with the aid of computer-based image analysis. Main Outcome Measures: Conventional clinicopathologic parameters and pSTAT3 expression were correlated with SCC prognosis. Results: pT, stage, and surgical margin status were significantly related with recurrence rate ( p = 0.002, p = 0.01, and p = 0.047, respectively) and disease-free survival (DFS) ( p = 0.0049, p = 0.031, and p = 0.035, respectively). pT classification was also related with disease-specific survival (DSS) ( p = 0.035). The SCC recurrence rate did not correlate with pSTAT3 ex- pression. Statistical analyses ruled out any significant difference in DFS or DSS when patients were stratified by pSTAT3 ex- pression (980.0% or e80.0%). Conclusion: Despite our preliminary results, the role of pSTAT3 in temporal bone SCC warrants further investigation in larger series because there is increasing evidence in preclin- ical models to indicate that inhibiting STAT3 phosphoryla- tion can be a useful addition to different anticancer strategies. Key Words: PrognosisVpSTAT3VSquamous cell carcinoma VTargeted therapyVTemporal bone. Otol Neurotol 34:1476Y1482, 2013. The estimated worldwide incidence of head and neck cancer for the year 2008, calculated by the International Agency for Research on Cancer (IARC) for 182 countries in 5 continents, was more than 630,000 new cases (making it the seventh most common human cancer) (1). Temporal bone squamous cell carcinoma (SCC) accounts for less than 0.2% of all tumors of the head and neck (2), but it is a distinctly aggressive malignancy. Although some progress has been made in the treatment of this disease over the decades, the prognosis remains poor (3), particularly for advanced cases. Multimodal therapy is considered essential for advanced tumors. Novel thera- peutic agents are needed, designed specifically to target temporal bone SCC. Targeting strategies should be used as an adjuvant for malignancies being treated with sur- gery, radiotherapy, and conventional chemotherapy with a view to improving tumor response and disease-specific survival rates, without adding to the burden of treatment- related toxicity. Address correspondence and reprint requests to Gino Marioni, M.D., Department of Neurosciences, Otolaryngology Section, Via Giustiniani 2, 35128 Padova, Italy; e-mail: gino.marioni@unipd.it The authors declare no conflicts of interest. This study was supported in part by Grant No. 60A07-3774/11 (G. M.) from the University of Padova, Italy. Otology & Neurotology 34:1476Y1482 Ó 2013, Otology & Neurotology, Inc. 1476 Copyright © 2013 Otology & Neurotology, Inc. Unauthorized reproduction of this article is prohibited.