Department of Pathology, Kurume University School of Medicine, Kurume, Japan
Department of Urology, Kurume University School of Medicine, Kurume, Japan.
Anticancer Res. 2019 Nov;39(11):6249-6257. doi: 10.21873/anticanres.13834.
BACKGROUND/AIM: Therapeutic targeting of receptor protein tyrosine kinases (PTKs) has proven successful in treating cancer. However, reports about PTKs in treating prostate cancer are few. Elevated expression of the erythropoietin-producing hepatocellular receptor A2 (EPHA2) receptor tyrosine kinase, a transmembrane protein, is associated with poor prognosis of certain cancer types when the enzyme is dephosphorylated. This study investigated whether EPHA2 is useful in predicting the biochemical recurrence of prostate cancer.
Data from 241 patients who had undergone total prostatectomy between 2007 and 2011 were used. EPHA2 protein expression was categorized as high or low by two pathologists. The relationship was examined between EPHA2 expression level (high vs. low) and clinicopathological factors including biochemical recurrence. Correlations were examined between EPHA2, low-molecular-weight protein tyrosine phosphatase (LMW-PTP), E-cadherin, and Ki-67.
EPHA2 expression was high in 121 (50.2%) and low in 120 (49.8%) patients. A log-rank test revealed early biochemical recurrence in the high-expression group. Gleason score, Ki-67 labeling index, and biochemical recurrence were more frequent in the high-expression group. Furthermore, multivariate analyses revealed that high EPHA2 expression was an independent prognostic factor for biochemical recurrence (hazard ratio=3.62, 95% confidence interval=2.39-5.61). Correlations between EPHA2 and both LMW-PTP and Ki-67 labeling index were positive, whereas EPHA2 and E-cadherin were negatively correlated.
EPHA2 overexpression is predictive of aggressive prostate cancer behavior. EPHA2 may be a powerful prognostic biomarker for decision-making in postoperative follow-up after total prostatectomy, and regarding the need for palliative treatment. Additionally, it may be an important therapeutic target.
背景/目的：受体酪氨酸激酶（PTKs）的治疗靶向已被证明可成功治疗癌症。然而，关于 PTKs 治疗前列腺癌的报道很少。促红细胞生成素产生肝细胞受体 A2（EPHA2）受体酪氨酸激酶的表达升高，当该酶去磷酸化时，与某些癌症类型的不良预后相关。本研究旨在探讨 EPHA2 是否可用于预测前列腺癌的生化复发。
使用了 2007 年至 2011 年间接受全前列腺切除术的 241 名患者的数据。两位病理学家将 EPHA2 蛋白表达分为高或低。检查 EPHA2 表达水平（高与低）与包括生化复发在内的临床病理因素之间的关系。检查了 EPHA2、低分子量蛋白酪氨酸磷酸酶（LMW-PTP）、E-钙粘蛋白和 Ki-67 之间的相关性。
EPHA2 表达高的患者有 121 例（50.2%），低的有 120 例（49.8%）。对数秩检验显示高表达组早期生化复发。高表达组的 Gleason 评分、Ki-67 标记指数和生化复发更为频繁。此外，多变量分析显示，高 EPHA2 表达是生化复发的独立预后因素（危险比=3.62，95%置信区间=2.39-5.61）。EPHA2 与 LMW-PTP 和 Ki-67 标记指数之间的相关性呈正相关，而 EPHA2 与 E-钙粘蛋白呈负相关。
EPHA2 过表达可预测前列腺癌的侵袭性行为。EPHA2 可能是全前列腺切除术后术后随访和姑息治疗决策的有力预后生物标志物。此外，它可能是一个重要的治疗靶点。
