Molecular Profiling and Prognostic Relevance of Circulating Tumor Cells in the Blood of Ovarian Cancer Patients at Primary Diagnosis and After Platinum-Based Chemotherapy
Molecular Profiling and Prognostic Relevance of Circulating Tumor Cells in the Blood of Ovarian Cancer Patients at Primary Diagnosis and After Platinum-Based Chemotherapy
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DOI：
10.1097/igc.0b013e318216cb91
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发表时间：
2011-07-01
影响因子：
4.8
通讯作者：
Wimberger, Pauline
中科院分区：
文献类型：
--
作者：
Aktas, Bahriye;Kasimir-Bauer, Sabine;Wimberger, Pauline
目的：骨髓中的播散性肿瘤细胞（DTC）对妇科恶性肿瘤的预后有重要意义。与抽血相比，骨髓穿刺不太被患者接受。在这项初步研究中，我们应用基于免疫磁性富集的AdnaTest BreastCancer，靶向上皮性妇科癌症的常见抗原，然后通过多重逆转录酶-聚合酶链反应选择和检测122名卵巢癌患者血液中的循环肿瘤细胞（CTC），这些患者在初步诊断和/或铂类药物化疗后。方法：在手术前（n = 86）和/或化疗后（n = 70）获得10毫升血液，并使用AdnaTest BreastCancer检测EpCAM-、MUC-1-和HER-2-转录物进行CTC分析。CA 125在额外的单重逆转录酶-聚合酶链反应中进行评估。结果：术前19%的患者检测到CTCs，其中EpCAM、MUC-1、HER-2和CA 125的阳性率分别为31%、50%、31%和50%。化疗后，CTC的总体检出率为27%，其中EpCAM（68%）、MUC-1（47%）、HER 2（21%）和CA 125（37%）。DTC在BM中的总体检出率在手术前为35%，在治疗后为31%。DTC和CTC之间的比较导致手术前和化疗后的一致率分别为59%和56%。CTC阳性与手术前（P = 0.0054）和化疗后（P = 0.047）较短的总生存期显著相关。结论：这种方法学方法可能有助于确定特异性生物治疗的分子靶点。血液分析可以提供补充DTC所获得的信息。
Objectives: Disseminated tumor cells (DTCs) in the bone marrow (BM) were shown to be of prognostic significance in gynecological cancers. Bone marrow aspiration is less accepted by patients compared with blood drawing. In this pilot study, we applied the AdnaTest BreastCancer based on immunomagnetic enrichment, targeting common antigens on epithelial gynecological cancers, followed by multiplex reverse transcriptase-polymerase chain reaction for selection and detection of circulating tumor cells (CTCs) in the blood of 122 ovarian cancer patients at primary diagnosis and/or after platinum-based chemotherapy. Results were compared with detection of DTC in BM.Methods: Ten-milliliter blood was obtained before surgery (n = 86) and/or after chemotherapy (n = 70) and analyzed for CTC with the AdnaTest BreastCancer for the detection of EpCAM-, MUC-1-, and HER-2-transcripts. CA 125 was assessed in an additional single-plex reverse transcriptase-polymerase chain reaction. Bone marrow aspirates were analyzed in duplicate by immunocytochemistry using the pan-cytokeratin antibody A45-B/B3.Results: Before surgery, CTCs were detected in 19% of patients, expressing EpCAM (31%), MUC-1 (50%), HER-2 (31%), and CA 125 (50%), respectively. After chemotherapy, the overall detection rate for CTC was 27%, thereof EpCAM (68%), MUC-1 (47%), HER2 (21%), and CA 125 (37%). The overall detection rate for DTC in the BM was 35% before surgery and 31% after therapy. A comparison between DTC and CTC resulted in a concordance rate of 59% before surgery and 56% after chemotherapy. CTC positivity significantly correlated with shorter overall survival before surgery (P = 0.0054) and after chemotherapy (P = 0.047).Conclusions: This methodological approach might help to identify molecular targets for specific biological therapies. Blood analysis could give additional information complimentary to that obtained by DTC.