title: Clinical usefulness of mitochondrial transcription factor A expression as a predictive marker in colorectal cancer patients treated with FOLFOX.
abstract: 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.
authors.affiliation: Department of Surgery, Osaka Rosai Hospital, Osaka, Japan. yy4160@yahoo.co.jp
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Yoshida
authors.forename: Junichi
authors.initials: J
authors.lastname: Hasegawa
authors.forename: Riichiro
authors.initials: R
authors.lastname: Nezu
authors.forename: Yong-Kook
authors.initials: YK
authors.lastname: Kim
authors.forename: Masaki
authors.initials: M
authors.lastname: Hirota
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Kawano
authors.forename: Hiroto
authors.initials: H
authors.lastname: Izumi
authors.forename: Kimitoshi
authors.initials: K
authors.lastname: Kohno
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D015179:Colorectal Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D004268:DNA-Binding Proteins / Q000032:analysis*; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D002955:Leucovorin / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000032:analysis*; D009944:Organoplatinum Compounds / Q000627:therapeutic use; D011379:Prognosis; D014157:Transcription Factors / Q000032:analysis*; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D024101:Mitochondrial Proteins; D009944:Organoplatinum Compounds; C499631:TFAM protein, human; D014157:Transcription Factors; D002955:Leucovorin; D005472:Fluorouracil