EpCAM-Expressing Circulating Tumor Cells in Colorectal Cancer

Background Several studies have raised the issue of the inadequacy of CellSearch® to detect the entire pool of circulating tumor cells (CTCs) from blood of cancer patients, suggesting that cells expressing low levels of epithelial cell adhesion molecule (EpCAM) are not recognized by the capture reagent. In this exploratory study, we aimed to evaluate the status of EpCAM in CTCs isolated from a group of metastatic colorectal cancer patients, in 40% of whom, CTC had been found to be undetected by the CellSearch® system. Methods CTCs were analyzed using both a microfiltration method (ScreenCell) and CellSearch® in parallel. Furthermore, since EpCAM exists in 2 different variants, we investigated the presence of both its intracellular domain (EpICD) and extracellular domain (EpEX) through immunofluorescence staining of CTCs on filters. Results Results from immunofluorescence experiments demonstrated that, overall, EpICD and/or EpEX was expressed in 176 CTCs detected by ScreenCell, while the CellSearch® system was able to capture only 10 CTCs. Conclusions This is the first demonstration that the low sensitivity of CellSearch® to detect CTCs in colorectal cancer patients is not due to the lack of EpCAM.

[1]  L. Terracciano,et al.  Predominant expression of truncated EpCAM is associated with a more aggressive phenotype and predicts poor overall survival in colorectal cancer , 2016, International journal of cancer.

[2]  Leon W M M Terstappen,et al.  Capture of Tumor Cells on Anti-EpCAM-Functionalized Poly(acrylic acid)-Coated Surfaces. , 2016, ACS applied materials & interfaces.

[3]  K. Pantel,et al.  Improved Detection of Circulating Tumor Cells in Metastatic Colorectal Cancer by the Combination of the CellSearch® System and the AdnaTest® , 2016, PloS one.

[4]  R. Salgado,et al.  Evaluation and consequences of heterogeneity in the circulating tumor cell compartment , 2016, Oncotarget.

[5]  Leon W M M Terstappen,et al.  Challenges in circulating tumor cell detection by the CellSearch system , 2016, Molecular oncology.

[6]  C. Nicolazzo,et al.  Circulating tumor cells isolation: the "post-EpCAM era". , 2015, Chinese journal of cancer research = Chung-kuo yen cheng yen chiu.

[7]  Yan Zhang,et al.  Capturing Cancer: Emerging Microfluidic Technologies for the Capture and Characterization of Circulating Tumor Cells. , 2015, Small.

[8]  E. Cortesi,et al.  The rationale for liquid biopsy in colorectal cancer: a focus on circulating tumor cells , 2015, Expert review of molecular diagnostics.

[9]  G. Járvás,et al.  Computational fluid dynamics-based design of a microfabricated cell capture device. , 2015, Journal of chromatographic science.

[10]  N. Stoecklein,et al.  Dynamic EpCAM expression on circulating and disseminating tumor cells: causes and consequences , 2014, Cellular and Molecular Life Sciences.

[11]  T. Price,et al.  Circulating tumour cells: the evolving concept and the inadequacy of their enrichment by EpCAM-based methodology for basic and clinical cancer research. , 2014, Annals of oncology : official journal of the European Society for Medical Oncology.

[12]  K. Pantel,et al.  Challenges in circulating tumour cell research , 2014, Nature Reviews Cancer.

[13]  B. Giepmans,et al.  EpCAM: structure and function in health and disease. , 2013, Biochimica et biophysica acta.

[14]  Chunsheng Jiang,et al.  Microfluidics and circulating tumor cells. , 2013, The Journal of molecular diagnostics : JMD.

[15]  A. Farcomeni,et al.  Prognostic value of circulating tumor cells in nonmuscle invasive bladder cancer: a CellSearch analysis. , 2012, Annals of oncology : official journal of the European Society for Medical Oncology.

[16]  L. Frati,et al.  Circulating tumor cells, colon cancer and bevacizumab: the meaning of zero. , 2011, Annals of oncology : official journal of the European Society for Medical Oncology.

[17]  M. Koch,et al.  Heterogeneous detection of circulating tumor cells in patients with colorectal cancer by immunomagnetic enrichment using different EpCAM-specific antibodies , 2010, BMC biotechnology.

[18]  Cinzia Marchese,et al.  The clinical application of autologous bioengineered skin based on a hyaluronic acid scaffold. , 2008, Biomaterials.

[19]  Jonathan W. Uhr,et al.  Tumor Cells Circulate in the Peripheral Blood of All Major Carcinomas but not in Healthy Subjects or Patients With Nonmalignant Diseases , 2004, Clinical Cancer Research.

[20]  G. Fleuren,et al.  Epidermal Growth Factor-Like Repeats Mediate Lateral and Reciprocal Interactions of Ep-CAM Molecules in Homophilic Adhesions , 2001, Molecular and Cellular Biology.

[21]  M Aizawa,et al.  Assembling of engineered IgG-binding protein on gold surface for highly oriented antibody immobilization. , 2000, Journal of biotechnology.