Department of Pathology, Karmanos Cancer Center, Wayne State University, Detroit, Michigan 48201, USA.
Gynecol Oncol. 2013 Feb;128(2):344-8. doi: 10.1016/j.ygyno.2012.07.128. Epub 2012 Aug 4.
The deregulation of E-cadherin is associated with Src/FAK signaling axis and histone deacetylase (HDAC)/EZH2 activity. However, the association between EZH2 and FAK and its clinical significance in endometrial carcinoma has not been reported.
202 archived cases of endometrial carcinoma (1996-2000) were reviewed and divided into two subtypes. TMAs were developed as per established procedures. EZH2, FAK, and pFAK immunohistochemical stains were performed and the expression was scored as negative (0), low (1) and high (2). Proper statistical analysis was used to assess the correlation between the expression profiles and the clinicopathological parameters and clinical outcome.
A total of 141 (69.8%) type-1 tumors and 61 (30.2%) type-2 tumors were identified. EZH2 overexpression was identified in 7.6% of type-1 tumors vs. 63% of type-2 tumors (p<0.001). FAK and pFAK overexpression was only seen in 24.8% and 1.7% of Type-1 tumors as compared to 72% and 58.8% of type-2 tumors, respectively (p<0.001). A positive correlation between the expression of EZH2, FAK, pFAK and PTEN (p<0.0001) was found. The overexpression of EZH2, FAK, and pFAK were significantly associated with high histologic grade, angiolymphatic invasion, lymph node metastasis, myometrial invasion and cervical involvement (p<0.01). Kaplan-Meier analysis demonstrates that the overexpression of EZH2 (p=0.0024), FAK and pFAK (p=0.0001) was significantly associated with decreased overall survival.
The overexpression of EZH2, FAK and pFAK correlates with well established pathologic risk factors and may predict a more aggressive biologic behavior in endometrial carcinoma, transforming these proteins into potential therapeutic targets for treatment of endometrial cancer.
E-钙黏蛋白的失调与Src/FAK 信号轴和组蛋白去乙酰化酶（HDAC）/EZH2 活性有关。然而，EZH2 与 FAK 的关联及其在子宫内膜癌中的临床意义尚未报道。
回顾了 202 例存档的子宫内膜癌病例（1996-2000 年），并将其分为两个亚型。按照既定程序制作 TMAs。进行 EZH2、FAK 和 pFAK 的免疫组织化学染色，并将表达评分记为阴性（0）、低（1）和高（2）。适当的统计分析用于评估表达谱与临床病理参数和临床结果之间的相关性。
共鉴定出 141 例（69.8%）1 型肿瘤和 61 例（30.2%）2 型肿瘤。在 1 型肿瘤中，EZH2 过表达的比例为 7.6%，而在 2 型肿瘤中为 63%（p<0.001）。仅在 24.8%和 1.7%的 1 型肿瘤中观察到 FAK 和 pFAK 的过表达，而在 72%和 58.8%的 2 型肿瘤中分别观察到 72%和 58.8%（p<0.001）。发现 EZH2、FAK 和 pFAK 的表达之间存在正相关（p<0.0001）。EZH2、FAK 和 pFAK 的过表达与高组织学分级、血管淋巴管侵犯、淋巴结转移、肌层浸润和宫颈受累显著相关（p<0.01）。Kaplan-Meier 分析表明，EZH2（p=0.0024）、FAK 和 pFAK 的过表达（p=0.0001）与总生存率降低显著相关。
EZH2、FAK 和 pFAK 的过表达与既定的病理危险因素相关，并可能预测子宫内膜癌更具侵袭性的生物学行为，使这些蛋白成为治疗子宫内膜癌的潜在治疗靶点。
