循环肿瘤细胞诊断乳腺癌实验的临床应用
Circulating Tumor Cells in Breast Cancer Patients: Measurement and Clinical Utility
循环肿瘤细胞诊断乳腺癌实验的临床应用
Herbert A. Fritsche, Ph.D.
M. D. Anderson Cancer Center
Houston, Texas
hfritsche@mdanderson.org
Current Concepts of Metastasis
? Cancer cells escape the confines of the tumor capsule
癌细胞从肿瘤灶逃逸
? Enter into the blood vessel 进入血管
? Circulate in the blood 在血液中循环
? Exit from the blood vessel 溢出血管
? Migrate to “favorable” metastatic site
转移到“合适的”新位点
Potential Clinical Utility
of CTC Detection
四氧化碳检测的临床应用前景
? Better disease staging, overt vs micro metastasic disease
更好的肿瘤转移分期，转移开始到确定
? New prognostic factor – assessing risk for metastastic relapse
新的预测因素-肿瘤转移复发风险因素的评估
? Predictive factor for chemotherapy (adjuvant or systemic)
化疗的预测因素
? Monitor for disease progression
疾病进展的监测
CTC Assay Types
CTC方法的类型
? Tumor cells are isolated from blood by positive or negative selection using column separation or immunomagnetic beads运用分离柱或免疫磁珠经过阳性和阴性选择分离出肿瘤细胞
~ Identified by antibody staining (IHC) and counted 通过抗体染色和计数鉴别肿瘤细胞
~ Characterized by expression of marker genes (RT-PCR)通过基因标志物表达来区分
? RT-PCR of whole blood is not a CTC assay
全血的RT-PCR 不属CTC方法
Commercially Available
CTC Assays 可从市场获得的CTC检测方法
1. Positive cell selection 阳性细胞分选
~ Veridex, Raritan, NJ
~ Adnagen, Longenhagen Germany
? Negative Cell Selection 阴性细胞分选
~ CCC Diagnostics, Baltimore, MD
~ CTC Inc, San Jose, CA
Veridex Cell Search System
? Immunomagnetic selection with anti-EPCAM免疫磁性分选
? IHC characterization with anti-pan cytokeratin (8, 18, 19) / Anti CD45
? Automated analysis with operator controlled counting of CTC计数自动分析
? FDA cleared FDA批准
CellSearch? System
细胞搜寻系统
Immunomagnetic CTC Selection 免疫磁性CTC分选
CellSearch? Intended Use
The CellSearch ? Epithelial Cell Kit is intended for
细胞搜寻系统上皮细胞试剂盒应用于：
? Enumeration of circulating tumor cells (CTCs)
循环肿瘤细胞的分选
? Predicting progression-free and overall survival in patients treated for metastatic breast cancer评价乳腺癌转移病人生存期病情进展
? Patients with >5 CTCs have significantly shorter progression-free and overall survival than those with <5 CTCs循环肿瘤细胞>5 的病人生存期远短于<5 病人
? 21 CFR 866.6020 Immunomagnetic Circulating Cancer Cell Selection and Enumeration System
21 CFR 866.6020免役磁性循环肿瘤细胞分选和计数系统
? Cristofanilli M et al N Engl J Med 2004;351:781-791
Predictive Value: OS of Patients
with < 5 or > 5 CTC at Baseline (N=177).
Predictive Value: OS Week 4-5
(1st Follow-Up) CTC cut-off at >5 CTC
Predictive Value: PFS
Week 4-5 (1st Follow-Up)
Predictive Value: Change in CTC Number
over 4-5 Weeks Predicts Overall Survival
