Open AccessClinical usefulness of mitochondrial transcription factor A expression as a predictive marker in colorectal cancer patients treated with FOLFOX
Author(s) -
Yoshida Yoichiro,
Hasegawa Junichi,
Nezu Riichiro,
Kim YongKook,
Hirota Masaki,
Kawano Kiyoshi,
Izumi Hiroto,
Kohno Kimitoshi
Publication year - 2011
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2010.01835.x
Subject(s) - tfam , oxaliplatin , fluorouracil , medicine , colorectal cancer , folfox , cisplatin , gastroenterology , folinic acid , chemotherapy , cancer , oncology , pathology , mitochondrial dna , biology , biochemistry , gene
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/m 2 ) plus leucovorin (200 mg/m 2 ) as a 2‐h infusion on day 1, followed by 5‐FU (400 mg/m 2 ) bolus and 46‐h continuous infusion of 2400 mg/m 2 . 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)