Capture And Molecular Characterization Of Ctc In Metastatic Breast, Prostate, Colorectal, And Renal Cancer

The most important determinant of prognosis and management of cancer is the incidence of metastasis. As a result, circulating tumor cell (CTC) detection and enumeration has been demonstrated to be a useful tool in assessing prognosis and monitoring therapeutic response. Current approaches to CTC detection largely depend on the antibody-mediated magnetic capture of the CTC using antibodies against the epithelial cell adhesion molecule (EpCAM), a feature which can be exploited in only a select few malignancies, and even in these cases, CTC capture is directly impacted by the variable expression of EpCAM. Responding to these issues, we have developed a novel parylene-based microfilter device for the capture, enumeration, and molecular characterization of CTC by exploiting size differences between larger epithelial tumor cells and smaller non-tumor blood cells. Our size-based approach, in contrast to immunoaffinity-based platforms, is ‘antigen expression-agnostic’; allowing analysis of diverse CTC populations and CTC from tumor types lacking target capture antigens. In the present study, the prospective collection of 500 blood samples from patients being treated at the Cleveland Clinic-Taussig Cancer Institute in Cleveland, OH is currently underway: 450 with advanced breast (BC), prostate (PC), and colorectal cancer (CRC) (150 from each disease site), and 50 with advanced renal cell carcinoma (RCC) and melanoma (25 from each disease site). To date, we have analyzed 28 patient blood samples by the microfilter device, of which 26 (92.8%) where positive for CTC (total at primary disease site, % samples positive, range of CTC detected) - BC: 1, 100%, 48; PC: 13, 84.6%, 1 to 144; CRC: 7, 100%, 18 to >500; RCC: 7, 100%, 1-128.* Further analysis demonstrates a number of interesting molecular characteristics on CTC, including heterogeneity in intensity of cytokeratin (CK) expression, differential patterns of CK staining on CTC (filamentous vs granular), and the occurrence of CTC as individual events or in clusters. Further, our data in blood samples from RCC demonstrate an ability to analyze CTC from non-EpCAM expressing tumor types, an area of study where many platforms have limited utility. With the ability to perform multiple, repeated sample analyses to detect recurrent disease early and enable drug response surveillance, we believe our technology has the potential to provide a faster, more efficient alternative to currently available methods for CTC analysis. The molecular characteristics on CTC we have identified herein could have critical biological relevance and implications for predicting aggressiveness of CTC and improving therapeutic monitoring. In ongoing studies, we are investigating the correlation of CTC enumeration, morphology, and clustering, with tumor type and treatment efficacy. *Data to be updated prior to presentation Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2372. doi:1538-7445.AM2012-2372