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Clinical usefulness of mitochondrial transcription factor A expression as a predictive marker in colorectal cancer patients treated with FOLFOX


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We previously reported that mitochondrial transcription factor A (mtTFA) preferentially recognizes cisplatin-damaged DNA via physical interaction with p53 and is upregulated by treatment with cisplatin and fluorouracil (5-FU). The aim of the present study was to evaluate whether expression of mtTFA predicts the clinical outcome in patients with metastatic colorectal cancer treated with modified 5-fluorouracil, leucovorin and oxaliplatin 6 (mFOLFOX6). Fifty-nine patients with metastatic lesions from colorectal cancer treated with mFOLFOX6 were included in this study. The subjects consisted of 25 women and 34 men with a median age of 62 years. The patients were treated with oxaliplatin (85 mg/m2) plus leucovorin (200 mg/m2) as a 2-h infusion on day 1, followed by 5-FU (400 mg/m2) bolus and 46-h continuous infusion of 2400 mg/m2. The expressions of mtTFA and p53 of resected primary tumors were examined by immunohistochemical analysis. Of the 59 patients, 33 (complete response 1, partial response 32) achieved a confirmed response to therapy. The positive cytoplasmic staining rate for mtTFA was 44.1% and that for p53 was 59.3%, respectively. Strong expression of mtTFA was detected in eight of 33 complete response/partial response (24.2%) and in 18 of 26 SD/PD (69.2%), indicating that mtTFA expression was significantly correlated with response to chemotherapy (P < 0.01). Median overall survival was significantly longer in patients without mtTFA expression (P = 0.0493). Multivariate analysis revealed that mtTFA expression significantly affected overall survival (hazard ratio 2.10, P = 0.036). Immunohistochemical study of mtTFA may be useful for predicting the clinical outcome of metastatic colorectal cancer patients treated with FOLFOX. (Cancer Sci 2011; 102: 578–582)