Abstract 6487: Circulating tumor cells, tumor- and endothelium- derived extracellular vesicles, but not circulating endothelial cells associate with poor prognosis in colorectal cancer

Molecular alterations are not randomly distributed in colorectal cancer (CRC), but rather clustered on the basis of primary tumor location underlying the importance of colorectal cancer sidedness. We aimed to investigate whether circulating tumor cells (CTC) characterization might help clarify how different the patterns of dissemination might be relative to the behavior of left- (LCC) compared to right-sided (RCC) cancers. We retrospectively analyzed patients with metastatic CRC who had undergone standard baseline CTC evaluation before starting any first-line systemic treatment. Enumeration of CTC in left- and right-sided tumors were compared. The highest prognostic impact was exerted by CTC in left-sided primary cancer patients, even though the lowest median number of cells was detected in this subgroup of patients. CTC exhibit phenotypic heterogeneity, with a predominant mesenchymal phenotype found in CTC from distal compared to proximal primary tumors. Most CTC in RCC patients exhibited an apoptotic pattern. CTC in left-sided colon cancer patients exhibit a predominant mesenchymal phenotype. This might imply a substantial difference in the biology of proximal and distal cancers, associated with different patterns of tumor cells dissemination. The poor prognosis of right-sided CRC is not determined by the hematogenous dissemination of tumor cells, which appears to be predominantly a passive shedding of non-viable cells. Conversely, the subgroup of poor-prognosis left-sided CRC is reliably identified by the presence of mesenchymal CTC.

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Early drop of circulating tumor cells (CTC) and increase of circulating endothelial cells (CEC) during neoadjuvant chemotherapy (CT) combined with bevacizumab in HER2-negative inflammatory breast cancer (IBC) in multicenter phase II trial BEVERLY 1.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.15_suppl.10510 ◽

2011 ◽

Vol 29 (15_suppl) ◽

pp. 10510-10510 ◽

Cited By ~ 2

Author(s):

J. Pierga ◽

F. Bidard ◽

F. Andre ◽

T. Petit ◽

F. Dalenc ◽

...

Keyword(s):

Breast Cancer ◽

Endothelial Cells ◽

Neoadjuvant Chemotherapy ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Phase Ii ◽

Inflammatory Breast Cancer ◽

Phase Ii Trial ◽

Circulating Endothelial Cells ◽

Multicenter Phase

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Association of mesenchymal phenotype in circulating tumor cells with poor prognosis in metastatic colorectal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e14567 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e14567-e14567

Author(s):

Arvind Dasari ◽

Hui Gao ◽

Laurel Deaton ◽

Michael J. Overman ◽

Siegfried Hauch ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Poor Prognosis ◽

Prognostic Significance ◽

Mesenchymal Transition ◽

Epithelial Markers ◽

Egfr Expression ◽

Aldh1 Expression

e14567 Background: Although the prognostic relevance of circulating tumor cells (CTCs) is well established in metastatic colorectal cancer (mCRC), their clinical use is currently constrained by the phenotypic definition of such cells that is largely limited to epithelial markers. Our objective in this study is to characterize the prognostic significance of a larger group of CTCs including those with characteristics of epithelial-mesenchymal transition (EMT) or cancer stem cells (CSCs) in a cohort of pre-treated mCRC patients (pts). Methods: Peripheral blood was collected in AdnaCollect preservation tubes from pts for immunomagnetic tumor cell enrichment using the AdnaTest ColonCancer Select kit and multiplex qRT-PCR analyses of tumor-associated epithelial (CEA, EPCAM, EGFR), cancer stem cell (ALDH1) and mesenchymal (TWIST1, AKT2, PIK3CA) transcripts. Results: In the initial phase, 41 previously treated mCRC pts (median prior therapies 3) were enrolled over a 4 month period and were followed prospectively. In this cohort, there was a low rate of CEA, EPCAM, and EGFR expression in the CTCs (12%, 2%, and 0%, respectively), consistent with loss of epithelial markers. Conversely, ALDH1, an established CSC marker was expressed in 30% of pts, with only one pt’s CTCs expressing both ALDH1 and CEA expression. ALDH1 expression was associated with very poor prognosis (HR 24.6, p=0.037) and 57% 60-day mortality, compared to 0% 60-day mortality for pts with no detectable ALDH1 expression. The mesenchymal markers of TWIST1, AKT2, and PIK3CA were strongly correlated with ALDH1 expression (Spearman r=0.55, 0.59, 0.63, respectively, p < 0.01 for each). Conclusions: The majority of CTCs detected in refractory mCRC pts have lost epithelial markers. Acquisition of markers associated with EMT or CSCs appear to be associated with poor prognosis, and may provide important insights into better prognostication and also biology of refractory colorectal cancer. Further enrolment into this study is ongoing and updated results will be presented.

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