分子标志物可预测直肠癌辅助放化疗后的远处转移。
Molecular markers predict distant metastases after adjuvant chemoradiation for rectal cancer.
机构信息
Department of Radiation Oncology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
出版信息
Int J Radiat Oncol Biol Phys. 2012 Dec 1;84(5):e577-84. doi: 10.1016/j.ijrobp.2012.07.2371. Epub 2012 Sep 14.
PURPOSE
The outcomes of adjuvant chemoradiation for locally advanced rectal cancer are nonuniform among patients with matching prognostic factors. We explored the role of molecular markers for predicting the outcome of adjuvant chemoradiation for rectal cancer patients.
METHODS AND MATERIALS
The study included 68 patients with stages II to III rectal adenocarcinoma who were treated with total mesorectal excision and adjuvant chemoradiation. Chemotherapy based on 5-fluorouracil and leucovorin was intravenously administered each month for 6-12 cycles. Radiation therapy consisted of 54 Gy delivered in 30 fractions. Immunostaining of surgical specimens for COX-2, EGFR, VEGF, thymidine synthase (TS), and Raf kinase inhibitor protein (RKIP) was performed.
RESULTS
The median follow-up was 65 months. Eight locoregional (11.8%) and 13 distant (19.1%) recurrences occurred. Five-year locoregional failure-free survival (LRFFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) rates for all patients were 83.9%, 78.7%, 66.7%, and 73.8%, respectively. LRFFS was not correlated with TNM stage, surgical margin, or any of the molecular markers. VEGF overexpression was significantly correlated with decreased DMFS (P=.045), while RKIP-positive results were correlated with increased DMFS (P=.025). In multivariate analyses, positive findings for COX-2 (COX-2+) and VEGF (VEGF+) and negative findings for RKIP (RKIP-) were independent prognostic factors for DMFS, DFS, and OS (P=.035, .014, and .007 for DMFS; .021, .010, and <.0001 for DFS; and .004, .012, and .001 for OS). The combination of both COX-2+ and VEGF+ (COX-2+/VEGF+) showed a strong correlation with decreased DFS (P=.007), and the combinations of RKIP+/COX-2- and RKIP+/VEGF- showed strong correlations with improved DFS compared with the rest of the patients (P=.001 and <.0001, respectively).
CONCLUSIONS
Molecular markers can be valuable in predicting treatment outcome of adjuvant chemoradiation for rectal cancer patients.
目的
局部晚期直肠癌患者的辅助放化疗结果存在不一致性，这与匹配的预后因素有关。本研究旨在探讨分子标志物在预测直肠癌患者辅助放化疗结果中的作用。
方法和材料
本研究纳入了 68 例 II 期至 III 期直肠腺癌患者，他们接受了全直肠系膜切除术和辅助放化疗。化疗方案为静脉注射氟尿嘧啶和亚叶酸，每月 1 次，共 6-12 个周期。放疗剂量为 54 Gy，共 30 次。对手术标本进行 COX-2、EGFR、VEGF、胸苷酸合成酶（TS）和 Raf 激酶抑制剂蛋白（RKIP）的免疫组化染色。
结果
中位随访时间为 65 个月。8 例（11.8%）出现局部区域复发，13 例（19.1%）出现远处转移。所有患者的 5 年局部区域无复发生存率（LRFFS）、无远处转移生存率（DMFS）、无病生存率（DFS）和总生存率（OS）分别为 83.9%、78.7%、66.7%和 73.8%。LRFFS 与 TNM 分期、手术切缘或任何分子标志物均无相关性。VEGF 过表达与较低的 DMFS 显著相关（P=.045），而 RKIP 阳性结果与较高的 DMFS 相关（P=.025）。多因素分析显示，COX-2（COX-2+）和 VEGF（VEGF+）阳性以及 RKIP（RKIP-）阴性是 DMFS、DFS 和 OS 的独立预后因素（P=.035、.014 和.007 用于 DMFS；P=.021、.010 和 <.0001 用于 DFS；P=.004、.012 和.001 用于 OS）。COX-2+/VEGF+的组合与较低的 DFS 显著相关（P=.007），而 RKIP+/COX-2-和 RKIP+/VEGF-的组合与其他患者相比，DFS 显著改善（P=.001 和 <.0001）。
结论
分子标志物可用于预测直肠癌患者辅助放化疗的治疗效果。
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