From the Departments of Pathology (Drs Xu and Brimo) and Urology (Drs Abourbih, Kassouf, Mansure, Aprikian, and Tanguay), McGill University Health Centre, Montreal, Quebec, Canada; and the Department of Pathology (Dr Sircar), The University of Texas Maryland Anderson Cancer Center, Houston.
Arch Pathol Lab Med. 2013 Oct;137(10):1326-36. doi: 10.5858/arpa.2012-0525-OA.
Enhancer of zeste homolog 2 (EZH2), a histone methyltransferase mediating chromatin condensation and epigenetic modulation, is overexpressed in various human carcinomas and is associated with adverse clinicopathologic characteristics and biologic behavior. The expression of EZH2 in renal cell carcinomas (RCCs) has not been fully characterized yet.
To evaluate the prognostic role of EZH2 in RCC by analyzing the immunohistochemical staining pattern of the marker in relation to pathologic features and clinical outcome.
We correlated the immunolabeling of EZH2 with multiple clinicopathologic features, including Fuhrman nuclear grade, pathologic stage, metastatic status, and clinical outcome in 223 clear cell RCCs (CRCCs) and 21 papillary RCCs, by using tissue microarrays of primary and metastatic cases.
Most CRCCs (75%) showed positive EZH2 staining, with most primary tumors showing focal staining in comparison to nonfocal staining in metastatic cases. In primary tumors, EZH2 expression was associated with higher nuclear grade and lower pathologic stage. Metastatic tumors showed a higher number of positive cases (81% versus 67%) and a more diffuse and more intense pattern of staining than primary CRCCs. For the 22 locally advanced primary tumors (T3/4) and 43 metastatic RCCs, patients who experienced RCC-related deaths significantly overexpressed the marker in comparison to patients who did not experience RCC-related mortality.
By showing that EZH2 expression is associated with increased metastatic potential and a worse clinical outcome, this study suggests that EZH2 can serve as a prognostic biomarker for RCC, thus confirming it as a key molecule driving oncogenesis and metastasis.
EZH2（增强子结合锌指蛋白 2）是一种组蛋白甲基转移酶，介导染色质凝聚和表观遗传调节，在各种人类癌中过表达，与不良的临床病理特征和生物学行为相关。EZH2 在肾细胞癌（RCC）中的表达尚未得到充分表征。
通过分析标志物的免疫组织化学染色模式与病理特征和临床结果的关系，评估 EZH2 在 RCC 中的预后作用。
我们使用原发性和转移性病例的组织微阵列，将 EZH2 的免疫标记与多个临床病理特征相关联，包括 Fuhrman 核分级、病理分期、转移状态和临床结果，共分析了 223 例透明细胞 RCC（CRCC）和 21 例乳头状 RCC。
大多数 CRCC（75%）显示 EZH2 染色阳性，与转移性病例相比，大多数原发性肿瘤显示局灶性染色而非非局灶性染色。在原发性肿瘤中，EZH2 的表达与更高的核分级和更低的病理分期相关。转移性肿瘤显示出更多的阳性病例（81%比 67%）和更弥漫和更强烈的染色模式。对于 22 例局部晚期原发性肿瘤（T3/4）和 43 例转移性 RCC，与未经历 RCC 相关死亡的患者相比，经历 RCC 相关死亡的患者显著过表达该标志物。
通过显示 EZH2 的表达与增加的转移潜能和更差的临床结果相关，本研究表明 EZH2 可作为 RCC 的预后生物标志物，从而证实其作为驱动致癌和转移的关键分子。
