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原发肿瘤切除对原发性乳腺癌循环肿瘤细胞发生率和表型的影响。

The influence of removal of primary tumor on incidence and phenotype of circulating tumor cells in primary breast cancer.

机构信息

Department of Obstetrics and Gynecology, University of Tuebingen, Calwerstrasse 7, 72076 Tuebingen, Germany.

出版信息

Breast Cancer Res Treat. 2012 Feb;132(1):121-9. doi: 10.1007/s10549-011-1569-0. Epub 2011 May 12.

DOI:10.1007/s10549-011-1569-0
PMID:21562707
Abstract

Recent studies have shown that the detection of circulating tumor cells (CTC) pre and postoperatively in the peripheral blood of primary breast cancer patients may be an indicator for poor survival. This study aimed to investigate the influence of removal of the primary tumor on incidence and phenotype of circulating tumor cells in primary breast cancer. 209 primary breast cancer patients could be included into this analysis. Blood sampling was performed both pre and postoperatively. The blood specimens were immunomagnetically enriched using AdnaTest BreastCancerSelect within 4 h after blood withdrawal, followed by RNA isolation and subsequent gene expression analysis by reverse transcription and multiplex PCR using AdnaTest BreastCancerDetect. Three breast cancer-associated tumor markers and two hormone receptor genes were amplified: GA733-2, Muc-1, Her-2, ER, PR. In addition, bone marrow (BM) status was intraoperatively determined. Forty-three of 209 patients (21%) had pre and/or postoperatively circulating tumor cells. The positivity rates after surgery were higher but did not differ significantly (12% pre and 16% postoperatively, P = 0.264). Disseminated tumor cells in BM were seen in 32 of 209 cases (15%). Patients with positive BM status had significantly higher CTC positivity rates both pre and postoperatively compared to those with negative BM status. The most common CTC phenotype was triple negative (24 patients) followed by HER2+/ER-/PR- subtype (10) and ER and/or PR positive (9). Interestingly, 41 of 43 primary tumors (95%) were ER and PR positive. Removal of the primary tumor did not alter the phenotype of CTC. Surgery does not significantly influence the tumor cell load in the blood stream. CTC phenotype before and after the surgery generally remains identical but may differ from that of the primary tumor.

摘要

最近的研究表明,检测原发性乳腺癌患者外周血中循环肿瘤细胞(CTC)术前和术后的情况可能是生存不良的指标。本研究旨在探讨原发性肿瘤切除对原发性乳腺癌患者循环肿瘤细胞发生率和表型的影响。209 例原发性乳腺癌患者可纳入本分析。在术前和术后均进行采血。采血后 4 小时内,使用 AdnaTest BreastCancerSelect 对血液标本进行免疫磁珠富集,随后进行 RNA 分离,并通过逆转录和多重 PCR 使用 AdnaTest BreastCancerDetect 进行基因表达分析。扩增了三个乳腺癌相关的肿瘤标志物和两个激素受体基因:GA733-2、Muc-1、Her-2、ER、PR。此外,术中还确定了骨髓(BM)状态。209 例患者中有 43 例(21%)术前和/或术后存在循环肿瘤细胞。术后的阳性率较高,但差异无统计学意义(术前 12%,术后 16%,P=0.264)。209 例中有 32 例(15%)可见 BM 中播散的肿瘤细胞。BM 状态阳性的患者术前和术后的 CTC 阳性率均明显高于 BM 状态阴性的患者。最常见的 CTC 表型是三阴性(24 例),其次是 HER2+/ER-/PR-亚型(10 例)和 ER 和/或 PR 阳性(9 例)。有趣的是,43 例 CTC 中有 41 例(95%)为 ER 和 PR 阳性。切除原发性肿瘤不会改变 CTC 的表型。手术不会显著影响血液中的肿瘤细胞负荷。手术前后 CTC 表型通常保持一致,但可能与原发性肿瘤不同。

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