The Initial Detection and Partial Characterization of Circulating Tumor Cells in Neuroendocrine Prostate Cancer.
The Initial Detection and Partial Characterization of Circulating Tumor Cells in Neuroendocrine Prostate Cancer.
复制标题
DOI：
10.1158/1078-0432.ccr-15-0137
复制
发表时间：
2016-03-15
期刊：
影响因子：
--
通讯作者：
Scher HI
中科院分区：
文献类型：
--
作者：
Beltran H;Jendrisak A;Landers M;Mosquera JM;Kossai M;Louw J;Krupa R;Graf RP;Schreiber NA;Nanus DM;Tagawa ST;Marrinucci D;Dittamore R;Scher HI
前列腺腺癌向主要为雄激素受体（AR）信号非依赖表型的转变可发生在疾病的后期，且与低AR表达和/或小细胞或神经内分泌肿瘤特征的发展有关。由于转移性肿瘤活检并不总是可行的，且难以重复，我们试图评估非侵入性方法来识别向神经内分泌表型（NEPC）转变的患者。
我们对去势抵抗性前列腺癌（CRPC）患者的转移性肿瘤活检、血清生物标志物和循环肿瘤细胞（CTC，Epic Sciences）进行了前瞻性研究，包括活检显示为纯NEPC或混合NEPC组织学的患者。用患者临床状态标记的CTC被用于了解区分NEPC患者的特征，然后将其应用于一个独立队列。
研究了27例CRPC患者，其中包括12例NEPC患者和5例具有提示NEPC转变的非典型临床特征的患者。与典型的CRPC相比，NEPC患者的CTC表现出频繁的聚集、低或无AR表达、较低的细胞角蛋白表达以及更小的形态。对蛋白质和形态学变量的多变量分析能够区分NEPC和CRPC的CTC。将这种CTC分类器应用于159例转移性CRPC患者的独立前瞻性队列，在159例中有17例（10.7%）被识别出来，在高CTC负荷（p<0.01）和内脏转移（p = 0.04）的患者中更为常见。
NEPC患者的CTC具有独特的形态学特征，这些特征也在一部分具有侵袭性临床特征且可能正在经历NEPC转变的CRPC患者中被识别出来。
The transition of prostate adenocarcinoma to a predominantly androgen receptor (AR) signaling independent phenotype can occur in the later stages of the disease and is associated with low AR expression and/or the development of small cell or neuroendocrine tumor characteristics. As metastatic tumor biopsies are not always feasible and are difficult to repeat, we sought to evaluate noninvasive methods to identify patients transitioning towards a neuroendocrine phenotype (NEPC). We prospectively studied a metastatic tumor biopsy, serum biomarkers and circulating tumor cells (CTC, Epic Sciences) from patients with castration resistant prostate cancer (CRPC) including those with pure or mixed NEPC histology present on biopsy. CTCs labeled with the patient’s clinical status were used to learn features that discriminate NEPC patients, which was then applied to an independent cohort. Twenty-seven patients with CRPC including 12 NEPC and 5 with atypical clinical features suggestive of NEPC transition were studied. CTCs from NEPC patients demonstrated frequent clusters, low or absent AR expression, lower cytokeratin expression, and smaller morphology relative to typical CRPC. A multivariate analysis of protein and morphologic variables enabled distinguishing CTCs of NEPC from CRPC. This CTC classifier was applied to an independent prospective cohort of 159 metastatic CRPC patients and identified in 17/159 (10.7%) of cases, enriched in patients with high CTC burden (p<0.01) and visceral metastases (p=0.04). CTCs from patients with NEPC have unique morphologic characteristics, which were also identified in a subset of CRPC patients with aggressive clinical features potentially undergoing NEPC transition.