Prediction of response to FOLFOX in metastatic colorectal cancer by mtTFA

Abstract

15079 Background: We previously reported that mitochondrial transcription factor A (mtTFA) preferentially recognizes cisplatin- damaged DNA via physical interaction with p53 and is upregulated by the treatment with cisplatin and 5-FU (Yoshida et al, Cancer Res. 2003). The aim of this study was to evaluate whether expression of mtTFA and/or p53 predicts clinical outcome in patients with metastatic colorectal cancer treated with modified FOLFOX6 (mFOLFOX6). Methods: From January 2006 to May 2007, 33 patients who had metastatic lesions from colorectal cancer treated with mFOLFOX6 at the Osaka Rosai Hospital were included in this study. They consisted of 18 women (54.5%) and 15 men (45.5%), with a median age of 64 years (29–84). Patients were treated with oxaliplatin 85mg/m2 plus leucovorin 200mg/m2 as a 2-h infusion at day 1, followed by 5-FU bolus 400mg/m2 and 46-h continuous infusion of 2400 mg/m2. Treatment was repeated in 2-week intervals for at least 5 cycles. The expressions of mtTFA and p53 of resected primary tumors were examined by immunohistochemistry. Results: Among 33 patients, 13 patients (CR 1, PR 12) achieved a confirmed response to therapy. The positive rates was 42.4% (14/33; CR 1, PR 1, SD/PD 12) for mtTFA and 57.6% (19/33; CR 1, PR 6, SD/PD 12) for p53, respectively. Strong expression of mtTFA was detected in 2 of 13 CR/PR (15.4%) and in 12 of 20 SD/PD (60%), indicating that the expression of mtTFA was significant negative correlation with respond to chemotherapy (P=0.011). On the other hand, there were no significant differences between response to chemotherapy and p53 expression pattern (P=0.727). Conclusions: Immunohistochemical studies for mtTFA may be useful in prediction of response to mFOLFOX6. No significant financial relationships to disclose.