M30 Neoepitope Expression in Epithelial Cancer: Quantification of Apoptosis in Circulating Tumor Cells by CellSearch Analysis
- 31 October 2010
- journal article
- research article
- Published by American Association for Cancer Research (AACR) in Clinical Cancer Research
- Vol. 16 (21), 5233-5243
- https://doi.org/10.1158/1078-0432.ccr-10-1449
Abstract
Purpose: This study aimed to detect the M30 neoepitope on circulating tumor cells (CTC) as a tool for quantifying apoptotic CTC throughout disease course and treatment. Experimental Design: An automated sample preparation and analysis platform for computing CTC (CellSearch) was integrated with a monoclonal antibody (M30) targeting a neoepitope disclosed by caspase cleavage at cytokeratin 18 (CK18) in early apoptosis. The assay was validated using cell lines and blood samples from healthy volunteers and patients with epithelial cancer. Results: M30-positive CTC could be detected in >70% of CTC-positive carcinoma patients, which were free for both chemotherapy and radiologic treatments. The fraction of M30-positive CTC varied from 50% to 80%, depending on the histotype. To investigate the potential application of the M30 CTC assay for the evaluation of response in early phase trials, CTC and M30-positive CTC were enumerated in a small case series of breast cancer patients during treatment. Results indicate that changes in the balance of M30-negative/positive CTC may be used as a dynamic parameter indicating an active disease, as documented by consistent radiologic findings. Conclusions: M30 expression on CTC is detectable by immunofluorescence. The M30-integrated test has potential for monitoring dynamic changes in the quote of apoptotic CTC (in addition to CTC count) to evaluate response in clinical trials of molecularly targeted anticancer therapeutics as well as for translational research, in which there is a pressing need for informative circulating biomarkers. Clin Cancer Res; 16(21); 5233–43. ©2010 AACR.Keywords
This publication has 29 references indexed in Scilit:
- All circulating EpCAM+CK+CD45- objects predict overall survival in castration-resistant prostate cancerAnnals of Oncology, 2010
- Improving the yield of circulating tumour cells facilitates molecular characterisation and recognition of discordant HER2 amplification in breast cancerBritish Journal of Cancer, 2010
- Detection of minimal residual disease in blood and bone marrow in early stage breast cancerCancer, 2010
- Changes in Circulating Tumor Cell Detection in Patients with Localized Breast Cancer Before and After SurgeryAnnals of Surgical Oncology, 2010
- Monitoring Drug-Induced γH2AX as a Pharmacodynamic Biomarker in Individual Circulating Tumor CellsClinical Cancer Research, 2010
- Evaluation of Circulating Tumor Cells and Serological Cell Death Biomarkers in Small Cell Lung Cancer Patients Undergoing ChemotherapyThe American Journal of Pathology, 2009
- Characterization of circulating tumor cells by fluorescence in situ hybridizationCytometry Part A, 2009
- Circulating and Disseminated Tumor Cells in the Clinical Management of Breast Cancer Patients: Unanswered QuestionsOncology, 2009
- Circulating Tumor Cells at Each Follow-up Time Point during Therapy of Metastatic Breast Cancer Patients Predict Progression-Free and Overall SurvivalClinical Cancer Research, 2006
- Circulating Tumor Cells, Disease Progression, and Survival in Metastatic Breast CancerThe New England Journal of Medicine, 2004