Department of Surgery, Osaka Rosai Hospital, Osaka, Japan.
Cancer Sci. 2011 Mar;102(3):578-82. doi: 10.1111/j.1349-7006.2010.01835.x. Epub 2011 Feb 1.
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.
我们之前报道过，线粒体转录因子 A（mtTFA）通过与 p53 的物理相互作用，优先识别顺铂损伤的 DNA，并且通过顺铂和氟尿嘧啶（5-FU）的处理而上调。本研究的目的是评估在接受改良的 5-氟尿嘧啶、亚叶酸钙和奥沙利铂 6（mFOLFOX6）治疗的转移性结直肠癌患者中，mtTFA 的表达是否可以预测临床结果。本研究纳入了 59 例接受 mFOLFOX6 治疗的转移性结直肠癌患者。这些患者包括 25 名女性和 34 名男性，中位年龄为 62 岁。患者接受奥沙利铂（85mg/m2）联合亚叶酸钙（200mg/m2）静脉滴注 2 小时，于第 1 天给药，随后给予 5-FU（400mg/m2）推注和 46 小时持续输注 2400mg/m2。通过免疫组织化学分析检测切除的原发肿瘤中 mtTFA 和 p53 的表达。在 59 例患者中，33 例（完全缓解 1 例，部分缓解 32 例）对治疗有明确的反应。mtTFA 的细胞质阳性染色率为 44.1%，p53 的阳性染色率为 59.3%。在 33 例完全缓解/部分缓解（24.2%）中检测到 8 例、在 26 例稳定/进展（69.2%）中检测到 18 例 mtTFA 强表达，表明 mtTFA 表达与化疗反应显著相关（P<0.01）。mtTFA 无表达患者的中位总生存期显著延长（P=0.0493）。多变量分析显示，mtTFA 表达显著影响总生存期（危险比 2.10，P=0.036）。mtTFA 的免疫组织化学研究可能有助于预测接受 FOLFOX 治疗的转移性结直肠癌患者的临床结果。
