TY - JOUR
T1 - M30 neoepitope expression in epithelial cancer
T2 - Quantification of apoptosis in circulating tumor cells by CellSearch analysis
AU - Rossi, Elisabetta
AU - Basso, Umberto
AU - Celadin, Romina
AU - Zilio, Francesca
AU - Pucciarelli, Salvatore
AU - Aieta, Michele
AU - Barile, Carmen
AU - Sava, Teodoro
AU - Bonciarelli, Giorgio
AU - Tumolo, Salvatore
AU - Ghiotto, Cristina
AU - Magro, Cristina
AU - Jirillo, Antonio
AU - Indraccolo, Stefano
AU - Amadori, Alberto
AU - Zamarchi, Rita
PY - 2010/11/1
Y1 - 2010/11/1
N2 - 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.
AB - 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.
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U2 - 10.1158/1078-0432.CCR-10-1449
DO - 10.1158/1078-0432.CCR-10-1449
M3 - Article
C2 - 20978147
AN - SCOPUS:78049485312
VL - 16
SP - 5233
EP - 5243
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 21
ER -