BCCIP: A novel marker for radiotherapy benefit in patients with laryngeal cancer

Abstract

6006 Background: It has been well established that the functionality of the p53 pathway is related to radiosensitivity in various human cancers. The status of proteins regulating p53 activity may also be valuable markers for radiosensitivity. Recent studies have shown that BCCIP (BRCA2 & CDKN1A interacting protein) is essential for maintaining the transactivation activity of wild type p53. We hypothesize that functional BCCIP may contribute to effective radiotherapy in the clinical setting. To test this hypothesis, we analyzed the expression of BCCIP and p53 in a cohort of laryngeal cancer treated with radiotherapy and assessed whether BCCIP and p53, alone or in combination, would correlate with local control and overall survival. Methods: One hundred thirty-five patients treated between 1975 and 2000 for early stage (stage I & II) squamous cell carcinoma of the larynx were included in the study. Treatment consisted of definitive radiation therapy (RT) with standard fields and fractionation to a median dose of 6,590 cGY. Tissue was collected from pre-RT biopsies and constructed in a tissue microarray, with duplicate cores created for each case. BCCIP and p53 expression was analyzed by immunohistochemistry and qualitatively scored with greater than 10% nuclear reactivity the cutoff for positive staining. Results: Expression of BCCIP and wild type p53 in combination was associated with significant improvements in 5-year local control (68.75% vs. 46.27%, p = .04) and 5-year overall survival (67.68% vs. 34.62%, p = .006) compared to patients who did not express BCCIP. Expression of BCCIP or p53 alone was not found to be independently associated with benefits in local control or overall survival. Conclusions: This study provides clinical evidence that BCCIP contributes to effective local control and overall survival in patients with laryngeal cancer treated with radiation. This benefit may be a result of increased radiosensitivity in patients who have functional BCCIP and p53. Using immunohistochemical methods, BCCIP and p53 co-expression can act as markers to identify sub-groups of laryngeal cancer patients who are more likely to be cured with radiotherapy. No significant financial relationships to disclose.