Department of Radiation Oncology, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan.
J Radiat Res. 2011;52(6):821-7. doi: 10.1269/jrr.11117.
Hypoxia-inducible factor 1α (HIF-1α) is an intrinsic marker of tumor hypoxia. It has been considered that hypoxic conditions reduce radiosensitivity, but the role of HIF-1α in patients treated with preoperative therapy for rectal cancer is still unclear. The aim of this study was to evaluate the predictive value of tumor response to preoperative hyperthermo-chemoradiotherapy (HCRT) and the prognostic significance of HIF-1α expression in patients with locally advanced rectal cancer. Between 2003 and 2006, 50 patients with histologically proven rectal adenocarcinoma who underwent HCRT followed by surgery were investigated. HIF-1α expression was immunohistochemically evaluated using pre-treatment biopsies. The total radiation dose was 40-50 Gy and chemotherapy consisted of 5-FU and LV administered by continuous infusion on Day 1-5, Day 15-19, and Day 29-33 during radiotherapy. Hyperthermia treatment was performed for once a week for 2-5 sessions. The surgical operation was performed 8 weeks after HCRT and each resected specimen was graded by histological criteria of the Japanese Classification of Colorectal Carcinoma. The effects of HIF-1α on clinical outcomes were analyzed by univariate and multivariate analysis. Positive HIF-1α expression was recognized in 42.0% of samples (21/50). Resected specimens that showed pathological grades 1, 2, and 3 numbered 17, 24, and 9 cases, respectively. There were no significant differences between the HIF-1α-positive group and HIF-1α-negative group for pathological grading and pCR. Overall survival (OS) rate at 3 years in the HIF-1α-negative group was 85.2%, which was significantly better than the 60.6% in the HIF-1α-positive group. Recurrence-free survival (RFS) rate at 3 years in the HIF-1α-negative group was 82.8%, being significantly better than 47.6% in the HIF-1α-positive group. In addition, elevated HIF-1α expression was significantly correlated with recurrence-free survival and metastasis-free survival rate in multivariate analysis. HIF-1α expression might be predictive of recurrence-free survival and metastasis-free survival rate for rectal cancer patients treated with HCRT.
缺氧诱导因子 1α（HIF-1α）是肿瘤缺氧的内在标志物。人们认为缺氧条件会降低放射敏感性，但 HIF-1α 在接受直肠癌术前治疗的患者中的作用尚不清楚。本研究旨在评估肿瘤对术前热化疗（HCRT）的反应预测价值以及局部晚期直肠癌患者中 HIF-1α表达的预后意义。2003 年至 2006 年间，对 50 例经组织学证实的直肠腺癌患者进行了 HCRT 加手术治疗。使用预处理活检进行 HIF-1α 表达的免疫组织化学评估。总辐射剂量为 40-50Gy，化疗包括 5-FU 和 LV，在放疗期间第 1-5 天、第 15-19 天和第 29-33 天持续输注。每周进行一次热疗，共 2-5 次。HCRT 后 8 周进行手术，每个切除标本按日本大肠癌分类的组织学标准进行分级。通过单因素和多因素分析分析 HIF-1α 对临床结果的影响。在 50 个样本中，有 42.0%（21/50）表现出阳性 HIF-1α 表达。显示病理分级 1、2 和 3 的切除标本分别为 17、24 和 9 例。HIF-1α 阳性组和 HIF-1α 阴性组在病理分级和 pCR 方面无显著差异。HIF-1α 阴性组 3 年总生存率（OS）为 85.2%，明显优于 HIF-1α 阳性组的 60.6%。HIF-1α 阴性组 3 年无复发生存率（RFS）为 82.8%，明显优于 HIF-1α 阳性组的 47.6%。此外，多因素分析显示，HIF-1α 高表达与无复发生存率和无转移生存率显著相关。HIF-1α 表达可能预测接受 HCRT 治疗的直肠癌患者的无复发生存率和无转移生存率。
