Expression of potential molecular markers in prostate cancer: Correlation with clinicopathological outcomes in patients undergoing radical prostatectomy
Expression of potential molecular markers in prostate cancer: Correlation with clinicopathological outcomes in patients undergoing radical prostatectomy
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DOI：
10.1016/j.urolonc.2008.08.001
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发表时间：
2010-03-01
影响因子：
2.7
通讯作者：
Fujisawa, Masato
中科院分区：
文献类型：
--
作者：
Miyake, Hideaki;Muramaki, Mototsugu;Fujisawa, Masato
本研究的目的是评估前列腺癌中多种潜在分子标志物的表达水平，以阐明这些标志物作为接受根治性前列腺癌切除术（RP）患者预后指标的意义。本研究共纳入了193例临床器官局限性前列腺癌患者，这些患者接受了RP，未接受任何新辅助治疗。采用免疫组化法检测193例RP组织中Ki-67、p53、雄激素受体（AR）、基质金属蛋白酶（MMP）-2、MMP-9、血管内皮生长因子、Aurora-A、Bcl-2、clusterin、热休克蛋白27（HSP 27）、HSP 70、HSP 90等12种蛋白的表达水平。在12种分子中，Ki-67、p53、AR、MMP-2、MMP-9和HSP 27的表达与几种常规预后因素显著相关。单因素分析表明，这6个标志物也是生化复发的重要预测因子，而前列腺特异性抗原、Gleason评分、精囊浸润（SVI）、手术切缘状态（SMS）、淋巴结转移和肿瘤体积也具有显著性。在这些重要因素中，Ki-67表达、SVI和SMS通过多变量分析与生化复发独立相关。此外，根据这三个独立危险因素的阳性数量，生化无复发生存率存在显著差异。这些研究结果表明，考虑潜在的分子标记物在RP标本的表达水平，除了传统的预后参数，将有助于准确预测生化复发RP后的临床局限性前列腺癌患者，并结合Ki-67表达，SVI和SMS的评价将是特别有用的进一步完善的系统在预测生化结果。(C)2010年爱思唯尔公司All rights reserved.
The objective of this study was to evaluate the expression levels of multiple potential molecular markers in prostate cancer to clarify the significance of these markers as prognostic indicators in patients undergoing radical prostatectomy (RP). This study included a total of 193 patients with clinically organ-confined prostate cancer who underwent RP without any neoadjuvant therapies. Expression levels of 12 proteins, including Ki-67, p53, androgen receptor (AR), matrix metalloproteinase (MMP)-2, MMP-9, vascular endothelial growth factor, Aurora-A, Bcl-2, clusterin, heat shock protein 27 (HSP27), HSP70, and HSP90, in RP specimens obtained from these 193 patients were measured by immunohistochemical staining. Of the 12 molecules, Ki-67, p53, AR, MMP-2, MMP-9, and HSP27 expression were significantly associated with several conventional prognostic factors. Univariate analysis identified these 6 markers as significant predictors for biochemical recurrence as well, while prostate-specific antigen, Gleason score, seminal vesicle invasion (SVI), surgical margin status (SMS), lymph node metastasis, and tumor volume were also significant. Of these significant factors, Ki-67 expression, SVI, and SMS appeared to be independently related to biochemical recurrence by multivariate analysis. Furthermore, there were significant differences in biochemical recurrence-free survival according to positive numbers of these three independent risk factors. These findings suggest that consideration of expression levels of potential molecular markers in RP specimens, in addition to conventional prognostic parameters, would contribute to accurate prediction of biochemical recurrence following RP in patients with clinically localized prostate cancer, and that combined evaluation of Ki-67 expression, SVI, and SMS would be particularly useful for further refinement of the system in predicting biochemical outcome. (C) 2010 Elsevier Inc. All rights reserved.