Expression of Human Epidermal Growth Factor Receptor-2 in Resected Rectal Cancer.
Expression of Human Epidermal Growth Factor Receptor-2 in Resected Rectal Cancer.
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人表皮生长因子受体2在直肠癌切除中的表达
DOI：
10.1097/md.0000000000002106
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发表时间：
2015-11
期刊：
影响因子：
1.6
通讯作者：
Xing L
中科院分区：
文献类型：
--
作者：
Meng X;Huang Z;Di J;Mu D;Wang Y;Zhao X;Zhao H;Zhu W;Li X;Kong L;Xing L
曲妥珠单抗联合化疗对晚期人表皮生长因子受体-2（HER-2）阳性胃癌的治疗是有益的。然而，直肠癌的HER-2状态仍然不确定。本研究的目的是确定HER-2表达在一个大型多中心队列的直肠癌患者。回顾性分析717例患者的临床及病理特点。所有患者均确诊为原发性直肠腺癌，无远处转移，术前未经任何抗癌治疗，直接手术治疗。对切除的样本评估HER-2状态。99例IHC 3+和16例IHC 2++基因扩增均为HER-2阳性。HER-2阳性患者局部复发率为22.6%，HER-2阴性患者局部复发率为16.9%（P = 0.146）。 HER-2表达阳性者远处转移率高（P = 0.007）。 单因素分析显示，肿瘤病理分期、病理淋巴结分期、切缘阳性和淋巴管浸润与5年无病生存率（DFS）和5年总生存率（OS）显著相关。清扫淋巴结>10个的患者OS显著延长（P = 0.045），但无DFS（P = 0.054）。 HER-2阴性组5年无病生存率（P < 0.001）和5年总生存率（P = 0.013）均显著高于HER-2阳性组。 在早期直肠癌和局部晚期直肠癌的亚组分析中，HER-2也是一个不良的生存预测因子。多因素分析显示HER-2是影响5年无病生存率（HR = 1.919，95% CI 1.415-2.605，P < 0.001）和5年总生存率（HR = 1.549，95% CI 1.097-2.186，P = 0.013）的独立预后因素。 当治疗纳入局部晚期患者的分析时，HER-2是5年DFS的预后因素（P = 0.001），但不是5年OS的预后因素（P = 0.106）。 本研究证实HER-2在部分直肠癌患者中有表达，可作为阴性预测指标。该结果可能支持评估曲妥珠单抗治疗HER-2阳性直肠癌患者的疗效的试验。
The addition of trastuzumab to chemotherapy was demonstrated to be beneficial for advanced human epidermal growth factor receptor-2 (HER-2) positive gastric cancer. However, the HER-2 status of rectal cancer remains uncertain. This study aimed to determine the HER-2 expression in a large multicenter cohort of rectal cancer patients. The clinical and pathological features of 717 patients were retrospectively reviewed. All the patients were diagnosed with primary rectal adenocarcinoma without distant metastasis and took surgery directly without any preoperative anticancer treatment. HER-2 status was assessed on resected samples. A total of 99 cases with IHC3+ and 16 cases with IHC 2+ plus gene amplification were determined as HER-2 positive. 22.6% of HER-2 positive patients had local recurrence, whereas 16.9% of HER-2 negative patients did (P = 0.146). HER-2 positive tumors were more likely to have distant metastasis (P = 0.007). Univariate analysis revealed that pathological tumor stage, pathological node stage, positive margin, and lymphovascular invasion were significantly correlated with 5-year disease-free survival (DFS) and 5-year overall survival (OS). The patients with >10 dissected lymph nodes showed significantly longer OS (P = 0.045) but not DFS (P = 0.054). HER-2 negative patients had significantly better 5-year DFS (P < 0.001) and 5-year OS (P = 0.013) than those of the HER-2 positive patients. In the subgroup analysis for the early rectal cancer and locally advanced rectal cancer, HER-2 was also a poor predictor for survival. Multivariate analysis revealed that HER-2 was an independent prognostic factor for 5-year DFS (hazard ratio [HR] = 1.919, 95% confidence interval [CI] 1.415–2.605, P < 0.001) and for 5-year OS (HR = 1.549, 95% CI 1.097–2.186, P = 0.013). When the treatment was included in the analysis for locally advanced patients, HER-2 was a prognostic factor for 5-year DFS (P = 0.001) but not for 5-year OS (P = 0.106). This study confirmed that HER-2 was expressed in a part of patients with rectal cancers and might be used as a negative predictor. The results may support the trials to assess the efficacy of trastuzumab in treating HER-2 positive rectal cancer patients.