早期乳腺癌腋窝淋巴结转移中循环肿瘤细胞的检测

Detection of circulating tumor cells in early-stage breast cancer metastasis to axillary lymph nodes.

作者信息

Nakagawa Taku, Martinez Steve R, Goto Yasufumi, Koyanagi Kazuo, Kitago Minoru, Shingai Tatsushi, Elashoff David A, Ye Xing, Singer Frederick R, Giuliano Armando E, Hoon Dave S B

机构信息

Department of Molecular Oncology, John Wayne Cancer Institute, Saint John's Health Center, Santa Monica, California 90404, USA.

出版信息

Clin Cancer Res. 2007 Jul 15;13(14):4105-10. doi: 10.1158/1078-0432.CCR-07-0419.

DOI:10.1158/1078-0432.CCR-07-0419

PMID:17634536

Abstract

PURPOSE

Clinical and pathologic prognostic factors do not always accurately predict disease outcome. Patients with early-stage breast cancer may harbor clinically significant but undetected systemic disease. We hypothesized that a multimarker quantitative real-time reverse transcription-PCR (qRT) assay could detect circulating tumor cells (CTC) in patients with early-stage breast cancer and correlate with sentinel lymph node (SLN) and non-SLN metastasis status.

EXPERIMENTAL DESIGN

Blood samples from 90 women with the American Joint Committee on Cancer stages I to III breast cancer and 39 age-matched normal healthy volunteers were assessed by qRT for mRNA expression of three markers: stanniocalcin-1 (STC-1), N-acetylgalactosaminyltransferase (GalNacT), and melanoma antigen gene family-A3 (MAGE-A3). CTC biomarker detection was correlated with overall axillary LN (ALN), SLN, and non-SLN histopathology status.

RESULTS

CTCs were detected in 39 of 90 (43%) patients, but not in normal volunteers. At least one CTC biomarker was detected in 10 of 35 (29%) stage I patients, 19 of 42 (45%) stage II patients, and 10 of 13 (77%) stage III patients. In multivariate analysis, only lymphovascular invasion and >or=2 CTC biomarkers detected significantly correlated with ALN metastasis [odds ratio (OR), 12.42; 95% confidence interval (95% CI), 3.52-43.77, P<0.0001; and OR, 3.88; 95% CI, 1.69-8.89, P=0.001, respectively]. The number of CTC biomarkers detected similarly correlated with SLN and non-SLN metastasis status (P=0.0004). At least one CTC biomarker was detected in 10 of 11 (91%) patients with non-SLN metastases.

CONCLUSION

The detection of CTCs offers a novel means to assess the presence of systemic disease spreading relative to SLN and ALN histopathology status.

摘要

目的

临床和病理预后因素并不总是能准确预测疾病结局。早期乳腺癌患者可能存在临床上显著但未被检测到的全身性疾病。我们假设一种多标志物定量实时逆转录聚合酶链反应（qRT）检测方法能够检测早期乳腺癌患者循环肿瘤细胞（CTC），并与前哨淋巴结（SLN）及非前哨淋巴结转移状态相关。

实验设计

对90例美国癌症联合委员会分期为I至III期的乳腺癌女性患者及39例年龄匹配的正常健康志愿者的血样进行qRT检测，分析三种标志物的mRNA表达：鲽钙蛋白-1（STC-1）、N-乙酰半乳糖胺基转移酶（GalNacT）和黑色素瘤抗原基因家族A3（MAGE-A3）。CTC生物标志物检测结果与腋窝淋巴结（ALN）、SLN及非SLN的组织病理学状态相关。

结果

90例患者中有39例（43%）检测到CTC，但正常志愿者中未检测到。I期35例患者中有10例（29%）、II期42例患者中有19例（45%）、III期13例患者中有10例（77%）检测到至少一种CTC生物标志物。多因素分析显示，仅淋巴管浸润及检测到≥2种CTC生物标志物与ALN转移显著相关[比值比（OR）分别为12.42；95%置信区间（95%CI）为3.52 - 43.77，P<0.0001；以及OR为3.88；95%CI为1.69 - 8.89，P = 0.001]。检测到的CTC生物标志物数量同样与SLN及非SLN转移状态相关（P = 0.0004）。11例非SLN转移患者中有10例（91%）检测到至少一种CTC生物标志物。