Mesh : Aged Antigens, CD Biomarkers, Tumor / analysis blood Biopsy Cadherins / analysis Disease-Free Survival Enhancer of Zeste Homolog 2 Protein / analysis Humans Immunohistochemistry Kallikreins / blood Kaplan-Meier Estimate Lymphatic Metastasis Male Middle Aged Neoplasm Grading Neoplasm Staging Nuclear Proteins / analysis Predictive Value of Tests Prostate-Specific Antigen / blood Prostatic Hyperplasia / metabolism pathology Prostatic Neoplasms / chemistry pathology therapy Retrospective Studies Time Factors Twist-Related Protein 1 / analysis Up-Regulation

来  源:   DOI:10.5146/tjpath.2016.01392   PDF(Sci-hub)

Abstract:
OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
摘要:
目的:迫切需要鉴定分子生物标记物,而不是临床标记物,以区分侵袭性前列腺癌和多数前列腺癌,以进行正确的治疗和准确的预后预测。我们旨在研究上皮间质转化(EMT)相关分子(Twist-1和E-cadherin)和干细胞标志物EZH2在前列腺癌中的免疫组化表达,并评估其识别高危患者的能力。在一项探讨其预后意义的试验中。
方法:研究了50例前列腺癌和20例良性前列腺增生标本中Twist-1,E-cadherin和EZH2的免疫组织化学表达。它们的表达与临床病理变量之间的关系,生化复发,和生化无进展生存期进行了调查。
结果:我们的结果表明,高Twist-1以及高EZH2表达,与较高的治疗前PSA水平密切相关,Gleason评分≥7分,肿瘤晚期,淋巴结受累,远处转移和生化进展。E-cadherin异常表达与较高的治疗前PSA水平显著相关,Gleason评分≥7分,肿瘤晚期,淋巴结受累,和远处转移。Twist-1和EZH2表达呈显著正相关(p<0.001),而E-cadherin表达与两种标志物均呈负相关(p<0.001)。发现高Twist-1,高EZH2和异常E-cadherin表达之间存在显着关联,和较短的生化无进展生存期。
结论:Twist-1高表达,原发性前列腺癌中E-cadherin异常和EZH2高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.评估其表达水平将有助于准确预测生化进展。
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