Wayne State University School of Medicine, Detroit, MI 48201, USA.
Hum Pathol. 2012 Oct;43(10):1638-44. doi: 10.1016/j.humpath.2011.12.004. Epub 2012 Mar 19.
The polycomb group protein, enhancer of zeste homolog 2, is a transcriptional repressor involved in cell cycle regulation and has been linked to aggressive breast cancer. We examined the clinical and biological significance of enhancer of zeste homolog 2 expression in triple-negative breast cancers. Tissue microarrays were constructed with invasive breast cancer cases and stained with the enhancer of zeste homolog 2, cytokeratin 5/6, epidermal growth factor receptor 1, and p53. The expression of these markers was correlated with clinicopathologic variables and patients' outcome. Furthermore, in vivo enhancer of zeste homolog 2 gene silencing was achieved using small interfering RNA incorporated into chitosan nanoparticles. Of 261 cases of invasive breast cancer, high expression of the enhancer of zeste homolog 2 was detected in 87 (33%) cases, and it was strongly associated with a triple-negative breast cancer phenotype (P < .001) compared with all other non-triple-negative breast cancers. Furthermore, high enhancer of zeste homolog 2 was significantly associated with high histologic grade (P = .01), estrogen receptor negativity (P < .001), progesterone receptor negativity (P < .001), epidermal growth factor receptor positivity (P = .04), and high p53 expression (P < .001). Survival analysis demonstrated that patients with high enhancer of zeste homolog 2 had a poorer overall survival compared with those with low enhancer of zeste homolog 2 (P = .03), and it retained its significance as an independent prognostic factor (P = .02). In addition, enhancer of zeste homolog 2 gene silencing resulted in a significant reduction in tumor growth (P < .01) in the orthotopic MB-231 mouse model of breast carcinoma. Our results show that high enhancer of zeste homolog 2 expression is significantly associated with triple-negative breast cancer and decreased survival. Enhancer of zeste homolog 2 may represent a potential therapeutic target for this aggressive disease, which warrants further investigation.
多梳蛋白增强子的锌指蛋白 2 是一种参与细胞周期调节的转录抑制剂，与侵袭性乳腺癌有关。我们研究了增强子的锌指蛋白 2 在三阴性乳腺癌中的表达的临床和生物学意义。用侵袭性乳腺癌病例构建组织微阵列，并与增强子的锌指蛋白 2、细胞角蛋白 5/6、表皮生长因子受体 1 和 p53 染色。这些标志物的表达与临床病理变量和患者的预后相关。此外，使用整合到壳聚糖纳米粒子中的小干扰 RNA 实现了体内增强子的锌指蛋白 2 基因沉默。在 261 例浸润性乳腺癌中，检测到 87 例（33%）增强子的锌指蛋白 2 高表达，与所有其他非三阴性乳腺癌相比，它与三阴性乳腺癌表型强烈相关（P <.001）。此外，高增强子的锌指蛋白 2 与高组织学分级显著相关（P =.01），雌激素受体阴性（P <.001），孕激素受体阴性（P <.001），表皮生长因子受体阳性（P =.04）和高 p53 表达（P <.001）。生存分析表明，与低表达的增强子的锌指蛋白 2 相比，高表达的增强子的锌指蛋白 2 患者总生存率较差（P =.03），并且它作为独立的预后因素仍然具有重要意义（P =.02）。此外，在乳腺癌的 MB-231 原位小鼠模型中，增强子的锌指蛋白 2 基因沉默导致肿瘤生长显著减少（P <.01）。我们的研究结果表明，高增强子的锌指蛋白 2 表达与三阴性乳腺癌和生存率降低显著相关。增强子的锌指蛋白 2 可能成为这种侵袭性疾病的潜在治疗靶点，值得进一步研究。
