Clinical Significance and Molecular Characteristics of Circulating Tumor Cells and Circulating Tumor Microemboli in Patients With Small-Cell Lung Cancer

被引：706

作者：

Hou, Jian-Mei ^{[1
]}

Krebs, Matthew G. ^{[1
,2
]}

Lancashire, Lee ^{[1
]}

Sloane, Robert ^{[1
]}

Backen, Alison ^{[1
]}

Swain, Rajeeb K. ^{[1
]}

Priest, Lynsey J. C. ^{[1
]}

Greystoke, Alastair ^{[1
]}

Zhou, Cong ^{[1
]}

Morris, Karen ^{[1
]}

Ward, Tim ^{[1
]}

Blackhall, Fiona H. ^{[1
,2
]}

Dive, Caroline ^{[1
]}

机构：

[1] Univ Manchester, Paterson Inst Canc Res, Clin & Expt Pharmacol Grp, Manchester Canc Res Ctr, Manchester M20 4BX, Lancs, England

[2] Christie Natl Hlth Serv Fdn Trust, Manchester, Lancs, England

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2012年 / 30卷 / 05期

关键词：

METASTATIC BREAST-CANCER; PERIPHERAL-BLOOD; COLORECTAL-CANCER; SURVIVAL; RECOMMENDATIONS; PROGRESSION; APOPTOSIS; CLUSTERS; LINES;

D O I：

10.1200/JCO.2010.33.3716

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Purpose Circulating tumor cells (CTCs) may have utility as surrogate biomarkers and "virtual" biopsies. We report the clinical significance and molecular characteristics of CTCs and CTC clusters, termed circulating tumor microemboli (CTM), detected in patients with small-cell lung cancer (SCLC) undergoing standard treatment. Patients and Methods Serial blood samples from 97 patients receiving chemotherapy were analyzed using EpCam-based immunomagnetic detection and a filtration-based technique. Proliferation status (Ki67) and apoptotic morphology were examined. Associations of CTC and CTM number with clinical factors and prognosis were determined. Results CTCs were present in 85% of patients (77 of 97 patients) and were abundant (mean +/- standard deviation = 1,589 +/- 5,565). CTM and apoptotic CTCs were correlated with total CTC number and were detected in 32% and 57% of patients, respectively. Pretreatment CTCs, change in CTC number after one cycle of chemotherapy, CTM, and apoptotic CTCs were independent prognostic factors. Overall survival was 5.4 months for patients with >= 50 CTCs/7.5 mL of blood and 11.5 months (P < .0001) for patients with less than 50 CTCs/7.5 mL of blood before chemotherapy (hazard ratio = 2.45; 95% CI, 1.39 to 4.30; P = .002). Subpopulations of apoptotic and of proliferating solitary CTCs were detected, whereas neither were observed within cell clusters (CTM), implicating both protection from anoikis and relative resistance to cytotoxic drugs for cells within CTM. Conclusion Both baseline CTC number and change in CTC number after one cycle of chemotherapy are independent prognostic factors for SCLC. Molecular comparison of CTCs to cells in CTM may provide novel insights into SCLC biology. J Clin Oncol 30: 525-532. (C) 2012 by American Society of Clinical Oncology

引用

页码：525 / 532

页数：8

共 31 条

[1] Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases [J].