Detection of mammaglobin mRNA in peripheral blood is associated with high grade breast cancer: interim results of a prospective cohort study.

Detection of mammaglobin mRNA in peripheral blood is associated with high grade breast cancer: interim results of a prospective cohort study.
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DOI:
10.1186/1471-2407-8-55
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发表时间:
2008-02-20
期刊:
影响因子:
3.8
通讯作者:
Cole DJ
Cole DJ
中科院分区:
医学2区
文献类型:
--
作者:
Mikhitarian K;Martin RH;Ruppel MB;Gillanders WE;Hoda R;Schutte del H;Callahan K;Mitas M;Cole DJ

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我们试图使用已建立的7基因标记物小组检查外周血(PBL)和骨髓(BM)中癌细胞的检测率,并评估是否有任何单个基因与传统的预后预测因素有明确的相关性。T1-T3原发乳腺癌患者被纳入一项前瞻性的多机构队列研究。在这项中期分析中,215个外周血和177个骨髓样本被用多标记实时RT-PCR分析,以检测循环和播散性乳腺癌细胞。以与正常对照组平均表达水平的三个标准差为阈值,63%(136/215)的PBL和11%(19/177)的骨髓样本至少有一个癌症相关标志物呈阳性。PBL中标志物的阳性与II-III级有统计学意义的相关性(vs.I级;p=0.0083)。单是乳巨球蛋白(Mam)基因的过度表达与高肿瘤分级有统计学意义的相关性(p=0.0315),并显示出向ER阴性肿瘤和高危类别发展的趋势。PBL标志物阳性与腋窝淋巴结(ALN)的病理(H&E)和(或)分子状态(RT-PCR)无关。本研究提示,RT-PCR检测PBL中循环癌细胞的分子水平与肿瘤的高分级有关,尤其是PBL中MAM基因的过度表达可能是一个不良的预后指标。PBL中癌相关基因的过度表达与ALN状态之间没有统计学意义的相关性,支持两条潜在的独立转移途径的概念。
We sought to examine the detection rate of cancer cells in peripheral blood (PBL) and in bone marrow (BM) using an established 7-gene marker panel and evaluated whether there were any definable associations of any individual gene with traditional predictors of prognosis. Patients with T1-T3 primary breast cancer were enrolled into a prospective, multi-institutional cohort study. In this interim analysis 215 PBL and 177 BM samples were analyzed by multimarker, real-time RT-PCR analysis designed to detect circulating and disseminated breast cancer cells. At a threshold of three standard deviations from the mean expression level of normal controls, 63% (136/215) of PBL and 11% (19/177) of BM samples were positive for at least one cancer-associated marker. Marker positivity in PBL demonstrated a statistically significant association with grade II-III (vs. grade I; p = 0.0083). Overexpression of the mammaglobin (mam) gene alone had a statistically significant association with high tumor grade (p = 0.0315), and showed a trend towards ER-negative tumors and a high risk category. There was no association between marker positivity in PBL and the pathologic (H&E) and/or molecular (RT-PCR) status of the axillary lymph nodes (ALN). This study suggests that molecular detection of circulating cancer cells in PBL detected by RT-PCR is associated with high tumor grade and specifically that overexpression of the mam gene in PBL may be a poor prognostic indicator. There was no statistically significant association between overexpression of cancer-associated genes in PBL and ALN status, supporting the concept of two potentially separate metastatic pathways.
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