Concurrent AURKA and MYCN Gene Amplifications Are Harbingers of Lethal TreatmentRelated Neuroendocrine Prostate Cancer
Concurrent AURKA and MYCN Gene Amplifications Are Harbingers of Lethal TreatmentRelated Neuroendocrine Prostate Cancer
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DOI：
10.1593/neo.121550
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发表时间：
2013-01-01
期刊：
影响因子：
4.8
通讯作者：
Rubin, Mark A.
中科院分区：
文献类型：
--
作者：
Mosquera, Juan Miguel;Beltran, Himisha;Rubin, Mark A.
神经内分泌前列腺癌（NEPC），也称为间变性前列腺癌，是一种致命的肿瘤，最常见于前列腺癌（PCA）的晚期，倾向于转移到内脏器官。在目前的研究中，我们探索极光激酶A（AURKA）和N-myc（MYCN）基因异常是治疗相关NEPC（t-NEPC）的先兆的证据。我们研究了来自15例激素初治前列腺癌、51例去势抵抗性前列腺癌和15例转移性肿瘤的原发性前列腺组织，这些肿瘤来自72例处于t-NEPC疾病进展不同阶段的患者，其中一些患者有多个标本。组织学评价，免疫组织化学，荧光原位杂交进行，并与临床变量。AURKA扩增在总体上65%的来自发展t-NEPC的患者的PCA（激素初治和治疗）和86%的转移瘤中被鉴定。MYCN的同时扩增存在于70%的原发性PCA、69%的治疗PCA和83%的转移瘤中。相比之下，在CAPCA队列中，AURKA和MYCN扩增仅在169例中的5%中被鉴定。当转移性t-NEPC与同一患者的原发性PCA比较时，ERG重排的一致性为100%，AURKA扩增的一致性为100%，MYCN扩增的一致性为60%。在具有混合特征的肿瘤中，NEPC和腺癌区域之间ERG重排的一致性为100%，AURKA和MYCN共扩增的一致性为94%。AURKA和MYCN扩增可能是预后和预测性生物标志物，因为它们是激素治疗后有进展为t-NEPC风险的肿瘤的先兆。
Neuroendocrine prostate cancer (NEPC), also referred to as anaplastic prostate cancer, is a lethal tumor that most commonly arises in late stages of prostate adenocarcinoma (PCA) with predilection to metastasize to visceral organs. In the current study, we explore for evidence that Aurora kinase A (AURKA) and N-myc (MYCN) gene abnormalities are harbingers of treatment-related NEPC (t-NEPC). We studied primary prostate tissue from 15 hormone naive PCAs, 51 castration-resistant prostate cancers, and 15 metastatic tumors from 72 patients at different stages of disease progression to t-NEPC, some with multiple specimens. Histologic evaluation, immunohistochemistry, and fluorescence in situ hybridization were performed and correlated with clinical variables. AURKA amplification was identified in overall 65% of PCAs (hormone naive and treated) from patients that developed t-NEPC and in 86% of metastases. Concurrent amplification of MYCN was present in 70% of primary PCAs, 69% of treated PCAs, and 83% of metastases. In contrast, in an unselected PCA cohort, AURKA and MYCN amplifications were identified in only 5% of 169 cases. When metastatic t-NEPC was compared to primary PCA from the same patients, there was 100% concordance of ERG rearrangement, 100% concordance of AURKA amplification, and 60% concordance of MYCN amplification. In tumors with mixed features, there was also 100% concordance of ERG rearrangement and 94% concordance of AURKA and MYCN co-amplification between areas of NEPC and adenocarcinoma. AURKA and MYCN amplifications may be prognostic and predictive biomarkers, as they are harbingers of tumors at risk of progressing to t-NEPC after hormonal therapy.