Clinical and biomarker correlates of androgen-independent, locally aggressive prostate cancer with limited metastatic potential
Clinical and biomarker correlates of androgen-independent, locally aggressive prostate cancer with limited metastatic potential
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DOI：
10.1158/1078-0432.ccr-04-0275
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发表时间：
2004-10-15
影响因子：
11.5
通讯作者：
McDonnell, TJ
中科院分区：
文献类型：
--
作者：
Assikis, VJ;Do, KA;McDonnell, TJ
目的：我们已经确定了一个亚群患者表现出延长生存与转移；从雄激素非依赖型前列腺癌的主要进展部位是肿瘤原发。本研究的目的是评估选定的生物标志物的表达，以表征前列腺癌患者的这一亚群。实验设计：采用16例原发肿瘤样本构建105核心组织微阵列，其中5例伴有匹配淋巴结转移。免疫组织化学用于评估与前列腺癌进展相关的选定生物标志物。使用标准统计方法计算进展时间分布和对生物标志物之间的总生存关联。在生物标志物组之间进行分层聚类，我们设计了新的方法来评估生物标志物表达的同质性。结果：从诊断到抢救手术的中位时间间隔为65个月。生物标志物的表达谱表现为神经内分泌特征的缺失、高CD10、低基质金属蛋白酶(MMP)-9、高E-cadherin表达和高膜β -连环蛋白表达。平均增殖指数为12.1 +/- 10.1%，平均凋亡指数为3.48 +/- 2.22%，两者之间存在显著相关性。表皮生长因子受体的表达与phospho-AKT和增殖指数相关，而与phospho-STAT3呈负相关。结论：前列腺癌患者队列的特点是局部侵袭性疾病，而不是致命的转移进展，与独特的生物标志物特征相关。总体而言，生物标志物谱更符合低级别前列腺癌表现为局部生长而非转移进展。正在进行的研究将确定这一独特的患者亚群是否可以前瞻性地识别出来。
Purpose: We have identified a subset of patients exhibiting extended survival with metastases; from androgen-independent prostate cancer of which the principal site of progression was the tumor primary. The purpose of this study was to evaluate the expression of selected biomarkers to characterize this subset of prostate cancer patients.Experimental Design: A 105 core tissue microarray was constructed from primary tumor samples from 16 patients, with matched lymph node metastases in 5 cases. Immuno-histochemistry was used to evaluate selected biomarkers associated with prostate cancer progression. Standard statistical methodologies were used to compute the distribution of time to progression and overall survival associations between pairs of biomarkers. Hierarchical clustering was done between groups of biomarkers, and we devised new methods to assess homogeneity of biomarker expression.Results: The median interval from diagnosis to salvage surgery was 65 months. The profile of biomarker expression was notable for virtual absence of neuroendocrine features, high CD10, low matrix metalloproteinase (MMP)-9, high E-cadherin expression, and high membranous beta-catenin. The mean proliferative index was 12.1 +/- 10.1%, and the mean apoptotic index was 3.48 +/- 2.22%, and there was a significant correlation between these indices. Expression of the epidermal growth factor receptor was associated with phospho-AKT and proliferative index but inversely associated with phospho-STAT3.Conclusions: The cohort of prostate cancer patients, characterized by locally aggressive disease rather than lethal metastatic progression, was associated with a distinctive biomarker signature. The biomarker profile was, in general, more consistent with low-grade prostate cancer exhibiting local growth rather than metastatic progression. Ongoing studies will establish whether this unique subset of patients can be identified prospectively.