Cancer and Clinical Oncology; Vol. 3, No. 1; 2014 ISSN 1927-4858 E-ISSN 1927-4866 Published by Canadian Center of Science and Education 11 Bcl-2 Family Gene Expression in Oropharyngeal Squamous Cell Carcinoma Jeremiah Tracy 1 , Ian Mukand-Cerro 2 , Miriam O’Leary 1 , Nora Laver 2 & Richard O. Wein 1 1 Department of Otolaryngology – Head and Neck Surgery, Tufts Medical Center, Boston, MA, USA 2 Department of Pathology and Laboratory Medicine, Tufts Medical Center, Boston, MA, USA Correspondence: Jeremiah Tracy, Tufts Medical Center, 800 Washington Street, Boston, MA 02111, USA. Tel: 1-617-636-5496. E-mail: jtracy@tuftsmedicalcenter.org Received: December 29, 2013 Accepted: January 28, 2014 Online Published: April 1, 2014 doi:10.5539/cco.v3n1p11 URL: http://dx.doi.org/10.5539/cco.v3n1p11 Abstract Dysregulation of apoptosis is a well-described characteristic of malignant transformation. In the field of colorectal cancer, the Bcl-2 family of apoptotic proteins has been characterized as a marker of poor prognosis and response to current chemotherapeutic agents. In head and neck squamous cell carcinoma (SCC), the role of Bcl-2 and associated apoptosis proteins is less well understood. Immunohistochemical staining was performed in order to assess for expression of Bcl-2, Bcl-Xl, and Bax in surgical or biopsy specimens of patients treated for oropharyngeal SCC from 1999-2009. This data was correlated with the clinical outcomes of recurrence and/or persistence of disease. Our findings on 20 specimens are presented. By establishing the association between these pathologic biomarkers and clinical characteristics of disease, more accurate diagnostic and prognostic tools will be available in the care of head and neck cancer patients. Keywords: head and neck cancer, oropharyngeal squamous cell carcinoma, Bcl-2, squamous cell carcinoma 1. Introduction Inhibition of the process of apoptosis is seen in most epithelial malignancies including squamous cell carcinoma (SCC) of the head and neck (Friedman et al., 1997). The B-cell lymphoma-2 (Bcl-2) gene is associated with a family of proteins involved in the regulation of apoptosis (Hockenbery, Nunez, Milliman, Schreiber, & Korsmeyer, 1990). This includes anti-apoptotic proteins such as Bcl-2 and Bcl-Xl and pro-apoptotic proteins such as Bax and Bad (Jackel, 1999). Dysregulation of Bcl-2 gene products, initially described as an inhibitor of apoptosis in B-cell lymphoma, has also been associated with other epithelial malignancies such as colorectal carcinoma. Subsequent studies demonstrated the over-expression of Bcl-2 in a subset of head and neck SCC tumors (Friedman et al., 1997; Jordan, Catzavelos, Barrett, & Speight, 1996). Since that time, several studies have suggested that Bcl-2 over-expression is associated with aggressive histopathologic features and advanced initial TNM tumor staging (Jordan et al., 1996; Pignataro et al., 1997; Sharma, Sen, Mathur, Bahadur, & Singh, 2004). Recent studies have suggested that tumors that overexpress Bcl-2 are less responsive to treatment with chemoradiation therapy and that Bcl-2 expression is an independent predictor of poor outcome (Trask et al., 2002; Nix, Cawkwell, Patmore, Greenman, & Stafford, 2005; Michaud et al., 2009; Shah et al., 2004; Nichols et al., 2010). The aim of this study was to correlate the expression of the Bcl-2 gene products with clinical outcomes in oropharyngeal SCC. The role of Bcl-Xl and Bax in head and neck SCC has yet to be elucidated definitively. In addition this study represents the first investigation into the relationship between Bcl-2 and the clinical course of patients that underwent surgery as part of their care as opposed to those treated with chemoradiation alone. 2. Materials and Methods Tissue-banked surgical specimens were used in order to investigate this correlation. Consecutive oropharyngeal SCC specimens that were obtained in the period from January 1, 1999 to December 31, 2009 were included. Experimental methods were reviewed and approved by the Tufts Medical Center Institutional Review Board. Initially, the specimens were stained using immunohistochemical (IHC) techniques to assess for expression of