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    Evaluation of circulating tumor cells and serological cell death biomarkers in small cell lung cancer patients undergoing chemotherapy.

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    Authors
    Hou, Jian-Mei
    Greystoke, Alastair
    Lancashire, Lee J
    Cummings, Jeffrey
    Ward, Timothy H
    Board, Ruth E
    Amir, Eitan
    Hughes, Sarah
    Krebs, Matthew G
    Hughes, Andrew
    Ranson, Malcolm R
    Lorigan, Paul C
    Dive, Caroline
    Blackhall, Fiona H
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    Affiliation
    Clinical and Experimental Pharmacology, Paterson Institute for Cancer Research, Wilmslow Road, Manchester, M20 4BX, UK.
    Issue Date
    2009-08
    
    Metadata
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    Abstract
    Serological cell death biomarkers and circulating tumor cells (CTCs) have potential uses as tools for pharmacodynamic blood-based assays and their subsequent application to early clinical trials. In this study, we evaluated both the expression and clinical significance of CTCs and serological cell death biomarkers in patients with small cell lung cancer. Blood samples from 88 patients were assayed using enzyme-linked immunosorbent assays for various cytokeratin 18 products (eg, M65, cell death, M30, and apoptosis) as well as nucleosomal DNA. CTCs (per 7.5 ml of blood) were quantified using Veridex CellSearch technology. Before therapeutic treatment, cell death biomarkers were elevated in patients compared with controls. CTCs were detected in 86% of patients; additionally, CD56 was detectable in CTCs, confirming their neoplastic origin. M30 levels correlated with the percentage of apoptotic CTCs. M30, M65, lactate dehydrogenase, and CTC number were prognostic for patient survival as determined by univariate analysis. Using multivariate analysis, both lactate dehydrogenase and M65 levels remained significant. CTC number fell following chemotherapy, whereas levels of serological cell death biomarkers peaked at 48 hours and fell by day 22, mirroring the tumor response. A 48-hour rise in nucleosomal DNA and M30 levels was associated with early response and severe toxicity, respectively. Our results provide a rationale to include the use of serological biomarkers and CTCs in early clinical trials of new agents for small cell lung cancer.
    Citation
    Evaluation of circulating tumor cells and serological cell death biomarkers in small cell lung cancer patients undergoing chemotherapy. 2009, 175 (2):808-16 Am. J. Pathol.
    Journal
    The American Journal of Pathology
    URI
    http://hdl.handle.net/10541/85377
    DOI
    10.2353/ajpath.2009.090078
    PubMed ID
    19628770
    Type
    Article
    Language
    en
    ISSN
    1525-2191
    ae974a485f413a2113503eed53cd6c53
    10.2353/ajpath.2009.090078
    Scopus Count
    Collections
    All Christie Publications
    All Paterson Institute for Cancer Research
    Clinical and Experimental Pharmacology Group
    Medical Oncology

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