Abdelrahman Aziza E, Arafa Shimaa A, Ahmed Ragab A
Department of Pathology, Zagazig University, Faculty of Medicine, ZAGAZIG, EGYPT.
Turk Patoloji Derg. 2017;1(1):198-210. doi: 10.5146/tjpath.2016.01392.
There is an urgent need to identify molecular biomarkers rather than clinical markers to distinguish aggressive prostate cancer from the indolent majority for proper treatment and accurate prediction of prognosis. We aimed to investigate the immunohistochemical expression of epithelial-mesenchymal transition (EMT)-related molecules (Twist-1 and E-cadherin) and the stem cell marker EZH2 in prostate cancer and to assess their ability to identify the high-risk patients, in a trial to explore their prognostic implications.
Immunohistochemical expression of Twist-1, E-cadherin and EZH2 in 50 specimens of prostate cancer and 20 cases of benign prostatic hyperplasia were studied. The relationship between their expression and the clinicopathological variables, biochemical recurrence, and biochemical progression-free survival were investigated.
Our results revealed that high Twist-1, as well as high EZH2 expression, was strongly associated with higher pre-treatment PSA level, Gleason score ≥7, advanced tumor stage, lymph node involvement, distant metastasis and biochemical progression. Aberrant E-cadherin expression was significantly associated with higher pre-treatment PSA level, Gleason score ≥7, advanced tumor stage, lymph node involvement, and distant metastasis. A significant positive correlation between Twist-1 and EZH2 expression was found (p < 0.001), while E-cadherin expression showed a negative correlation with both markers (p < 0.001). A significant association was found between high Twist-1, high EZH2& aberrant E-cadherin expression, and shorter biochemical progression-free survival.
The high Twist-1 expression, aberrant E-cadherin and high EZH2 expression in primary prostate cancer are considered as adverse prognostic markers of an aggressive tumor with high metastatic potential. Assessment of their expression level would contribute to the accurate prediction of biochemical progression.
迫切需要识别分子生物标志物而非临床标志物，以区分侵袭性前列腺癌与大多数惰性前列腺癌，从而进行恰当治疗并准确预测预后。我们旨在研究上皮-间质转化（EMT）相关分子（Twist-1和E-钙黏蛋白）及干细胞标志物EZH2在前列腺癌中的免疫组化表达，并评估它们识别高危患者的能力，以探索其预后意义。
研究了50例前列腺癌标本和20例良性前列腺增生病例中Twist-1、E-钙黏蛋白和EZH2的免疫组化表达。研究了它们的表达与临床病理变量、生化复发及无生化进展生存期之间的关系。
我们的结果显示，高Twist-1以及高EZH2表达与治疗前较高的前列腺特异性抗原（PSA）水平、 Gleason评分≥7、肿瘤晚期、淋巴结受累、远处转移及生化进展密切相关。E-钙黏蛋白表达异常与治疗前较高的PSA水平、Gleason评分≥7、肿瘤晚期、淋巴结受累及远处转移显著相关。发现Twist-1与EZH2表达之间存在显著正相关（p < 0.001），而E-钙黏蛋白表达与这两种标志物均呈负相关（p < 0.001）。发现高Twist-1、高EZH2及E-钙黏蛋白表达异常与较短的无生化进展生存期之间存在显著关联。
原发性前列腺癌中高Twist-1表达、E-钙黏蛋白表达异常及高EZH2表达被认为是具有高转移潜能的侵袭性肿瘤的不良预后标志物。评估它们的表达水平将有助于准确预测生化进展。
