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The prognosis for patients with squamous cell carcinoma of the head and neck remains poor, despite refinements in conventional therapy and experimental protocols using alternative treatment modalities. Identifying biomarkers with predictive potential to choose therapeutic strategies for patients will tremendously benefit the patients and improve their quality of life and survival. We have previously shown that p53 mutation status and Bcl-xL expression correlate with cisplatin sensitivity in head and neck squamous cell carcinoma (HNSCC) cell lines. In the present study, the expression profiles of p53 and Bcl-xL in 42 patients with advanced oropharyngeal cancer enrolled in an organ preservation clinical trial were analyzed and their correlation with chemotherapy response, organ preservation and survival determined. Patients received one cycle of cisplatin and 5-fluorouracil. Patients achieving 50% reduction of their primary tumor size received concurrent chemoradiation; those with less than 50% response underwent definitive surgery and adjuvant radiation. Chemoradiation consisted of 70 Gy (2 Gy fraction daily × 7 weeks) with concurrent cisplatin 100 mg/m2 every 3 weeks × 3 cycles. A tissue microarray was constructed from pre-treatment tumor biopsies and immunohistologic expression of p53 and Bcl-xL was determined. Proportion of p53 and Bcl-xL positive tumor cells were scored by a pathologist as <5%, 5-20%, 21-50%, and >50%. Patients were grouped into 4 categories based on combinations of p53 high (>5%) or low (<5%) and Bcl-xL high (>21%) or low (<20%). There were significant differences between the 4 groups in overall survival (p=0.01) and disease-free survival (p=0.04). Patients with tumors having both low p53 expression and high Bcl-xL expression had the poorest overall and disease free survival. In contrast, patients with tumors having low p53 and low Bcl-xL staining had the best overall survival and lowest risk of recurrence. No difference in response to induction chemotherapy or organ preservation was observed. These results suggest that Bcl-xL expression in patients with tumors having low p53 expression could identify patients with poor response to a chemoradiation treatment approach. Targeting the anti-apoptotic protein, Bcl-xL, with small molecular inhibitors along with conventional chemotherapeutic agents could be a strategy to improve outcome and treatment selection in patients with biologically aggressive oropharyngeal cancer. This research is supported by NIH NIDCR grants (R01 DE13346) & (P30 DC 05188), University of Michigan’s Head and Neck Cancer SPORE grant (P50 CA97248) & Cancer Center Support Grant (P30 CA46592).

[Proc Amer Assoc Cancer Res, Volume 47, 2006]