PTEN loss in circulating tumour cells correlates with PTEN loss in fresh tumour tissue from castration-resistant prostate cancer patients.
PTEN loss in circulating tumour cells correlates with PTEN loss in fresh tumour tissue from castration-resistant prostate cancer patients.
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DOI：
10.1038/bjc.2015.332
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发表时间：
2015-10-20
影响因子：
8.8
通讯作者：
de Bono J
中科院分区：
文献类型：
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作者：
Punnoose EA;Ferraldeschi R;Szafer-Glusman E;Tucker EK;Mohan S;Flohr P;Riisnaes R;Miranda S;Figueiredo I;Rodrigues DN;Omlin A;Pezaro C;Zhu J;Amler L;Patel P;Yan Y;Bales N;Werner SL;Louw J;Pandita A;Marrinucci D;Attard G;de Bono J
PTEN基因丢失经常发生在去势抵抗性前列腺癌（CRPC）中，并可能通过激活PI 3 K/AKT途径推动进展。在这里，我们开发了一种新的基于CTC的检测方法来确定PTEN状态，并检查了CTC和匹配的肿瘤组织样本中PTEN状态之间的相关性。在无富集平台（Epic Sciences）上通过荧光原位杂交（FISH）评估CTC中的PTEN基因状态。通过FISH和免疫组化评价存档和新鲜肿瘤组织中的PTEN状态。收集76例患者的外周血。匹配的档案和新鲜的癌组织可用于48例患者。CTCs中检测到的PTEN基因状态分别与38例患者中的32例（84%）和39例患者中的24例（62%）的匹配新鲜组织和存档组织中的PTEN状态一致。CTC计数具有预后性（连续，P=0.001）。在单变量分析中，CTC中的PTEN丢失与更差的存活率相关（HR 2.05; 95%CI 1.17-3.62; P=0.01），并且在转移性CRPC患者中与高乳酸脱氢酶（LDH）相关。我们的研究结果说明了CTC作为非侵入性实时液体活检来确定PTEN基因状态的潜在用途。PTEN在CTC中的预后和预测价值值得在PI 3 K/AKT靶向疗法的CRPC临床试验中进行研究。
PTEN gene loss occurs frequently in castration-resistant prostate cancer (CRPC) and may drive progression through activation of the PI3K/AKT pathway. Here, we developed a novel CTC-based assay to determine PTEN status and examined the correlation between PTEN status in CTCs and matched tumour tissue samples. PTEN gene status in CTCs was evaluated on an enrichment-free platform (Epic Sciences) by fluorescence in situ hybridisation (FISH). PTEN status in archival and fresh tumour tissue was evaluated by FISH and immunohistochemistry. Peripheral blood was collected from 76 patients. Matched archival and fresh cancer tissue was available for 48 patients. PTEN gene status detected in CTCs was concordant with PTEN status in matched fresh tissues and archival tissue in 32 of 38 patients (84%) and 24 of 39 patients (62%), respectively. CTC counts were prognostic (continuous, P=0.001). PTEN loss in CTCs associated with worse survival in univariate analysis (HR 2.05; 95% CI 1.17–3.62; P=0.01) and with high lactate dehydrogenase (LDH) in metastatic CRPC patients. Our results illustrate the potential use of CTCs as a non-invasive, real-time liquid biopsy to determine PTEN gene status. The prognostic and predictive value of PTEN in CTCs warrants investigation in CRPC clinical trials of PI3K/AKT-targeted therapies.