Department of Public Health Sciences, Henry Ford Hospital, Detroit, MI, USA.
Breast Cancer Res Treat. 2012 Apr;132(2):429-37. doi: 10.1007/s10549-011-1591-2. Epub 2011 May 26.
The identification of women with early-stage breast cancer who will develop distant metastasis may improve clinical management. The transcriptional regulator Enhancer of Zeste-2 (EZH2) is overexpressed in invasive breast carcinoma compared with benign breast tissues, with maximal expression in breast cancer metastasis. In this article, our purpose was to investigate the performance of EZH2 protein detection as a predictor of metastasis in women with early-stage breast cancer, which is unknown. We developed a cohort of 480 women with stage I-IIA breast cancer diagnosed between 1996 and 2002 and recorded detailed sociodemographic, clinical, and pathological information. Tumors were histologically characterized and arrayed in tissue microarrays containing 1,443 samples. The nuclear EZH2 expression was investigated by immunohistochemistry and was scored as 1-2 (negative and weak) or 3-4 (moderate and strong) using a validated scoring schema. Scores 1-2 were considered low EZH2; scores 3-4 were considered high EZH2. In this study, we found that after a median follow up of 9 years (range 0.04-14.5 years) 46 of 480 patients (9.6%) developed distant metastasis. High EZH2 was associated with larger size, high histological grade, negative hormone receptors, and first degree family history of breast and/or ovarian carcinoma. While EZH2 could not predict survival in the entire cohort, high EZH2 was a predictor of disease-specific survival in patients with early-stage disease and first degree family history (log rank P value 0.05). Importantly, in this group of patients, high EZH2 was an independent predictor of distant metastasis up to 15 years after primary carcinoma diagnosis (hazard ratio 6.58, 95% CI: 1.40-30.89, P = 0.016) providing survival information above and beyond currently used prognosticators. In conclusion, EZH2 may be a useful biomarker of long-term metastatic risk in women with familial early-stage breast cancer, and warrant further validation studies.
早期乳腺癌患者中，确定哪些患者会发生远处转移，可能有助于改善临床管理。转录调控因子 Enhancer of Zeste-2（EZH2）在浸润性乳腺癌中表达高于良性乳腺组织，在乳腺癌转移中表达最高。本文旨在研究 EZH2 蛋白检测作为早期乳腺癌患者转移预测指标的性能，这方面的信息尚不清楚。我们建立了一个队列，其中包括 480 名 1996 年至 2002 年间诊断为 I 期-IIA 期乳腺癌的女性，记录了详细的社会人口统计学、临床和病理信息。肿瘤组织经组织学特征分析，并排列在包含 1443 个样本的组织微阵列中。采用经过验证的评分方案，通过免疫组织化学检测核 EZH2 表达，并将评分分为 1-2（阴性和弱阳性）或 3-4（中-强阳性）。评分 1-2 为低 EZH2；评分 3-4 为高 EZH2。本研究发现，在中位随访 9 年（范围 0.04-14.5 年）后，480 例患者中有 46 例（9.6%）发生远处转移。高 EZH2 与肿瘤较大、组织学分级较高、激素受体阴性以及一级亲属有乳腺癌和/或卵巢癌病史相关。尽管 EZH2 不能预测整个队列的生存情况，但在早期疾病和一级亲属史的患者中，EZH2 是疾病特异性生存的预测因子（对数秩检验 P 值 0.05）。重要的是，在这群患者中，高 EZH2 是原发性乳腺癌诊断后 15 年内远处转移的独立预测因子（风险比 6.58，95%CI：1.40-30.89，P=0.016），提供了比目前使用的预后指标更有价值的生存信息。总之，EZH2 可能是具有家族性早期乳腺癌的女性发生长期转移风险的有用生物标志物，值得进一步验证研究。
