Combined evaluation of Rad51 and ERCC1 expressions for sensitivity to platinum agents in non-small cell lung cancer (NSCLC)

18085 Background: DNA repair enzyme expression in tumor cells possibly affects sensitivity to anti-cancer agents. The aim of this study was to determine the relationship between expression status of DNA repair proteins and chemosensitivity in patients with NSCLC. Rad51 and ERCC1 play important roles in repair of double and single strand breaks of DNA, respectively, and may protect cells from cytotoxic effect of platinum agents. Methods: NSCLC tissues prepared from the surgical specimens of 41 patients were subjected to an immunohistochemical analysis for Rad51 and ERCC1 proteins and to a chemosensitivity test using the MTT assay. The relationships between the expression status of the DNA repair enzymes and ex vivo chemosensitivity to various agents were evaluated. Results: A positive expression for Rad51 and ERCC1 was observed in 17 cases (41%) and 20 cases (49%), respectively. The positivity of Rad51 was closely related to a certain histologic type of squamous cell carcinoma and poor differentiation, and the positivity of ERCC1 tended to be related to squamous cell carcinoma. In chemosensitivity tests, sensitivities to CDDP and CBDCA were significantly lower when both two enzymes were positive (p = 0.012 and 0.04 in CDDP, 0.014 and 0.03 in CBDCA), but not when either or neither of them was positive. Both Rad51 and ERCC1 expressions showed no significant relationship with sensitivities to paclitaxel, etoposide, vinorelbine, gemcitabine, 5-FU, or irinotecan. Conclusions: Combined expression of Rad51 and ERCC1 is associated with resistance to platinum agents in the ex vivo study of clinical NSCLC, and evaluation of expression status of both DNA repair enzymes would be a predictor for clinical response to platinum-based chemotherapies. No significant financial relationships to disclose.