Development of a novel c-MET-Based CTC detection platform

Tian Zhang, Rengasamy Boominathan, Brad Foulk, Chandra Rao, Gabor Kemeny, John H. Strickler, James L. Abbruzzese, Michael R. Harrison, David S. Hsu, Patrick Healy, Jing Li, Cinthia Pi, Katherine M. Prendergast, Carey Hobbs, Sarah Gemberling, Daniel J. George, Herbert I. Hurwitz, Mark Connelly, Mariano Garcia-Blanco, Andrew J. Armstrong

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16 Scopus citations

Abstract

Amplification of the MET oncogene is associated with poor prognosis, metastatic dissemination, and drug resistance in many malignancies. We developed a method to capture and characterize circulating tumor cells (CTC) expressing c-MET using a ferromagnetic antibody. Immunofluorescence was used to characterize cells for c-MET, DAPI, and pan-CK, excluding CD45 leukocytes. The assay was validated using appropriate cell line controls spiked into peripheral blood collected from healthy volunteers (HV). In addition, peripheral blood was analyzed from patients with metastatic gastric, pancreatic, colorectal, bladder, renal, or prostate cancers. CTCs captured by c-MET were enumerated, and DNA FISH for MET amplification was performed. The approach was highly sensitive (80%) for MET-amplified cells, sensitive (40%-80%) for c-MET-overexpressed cells, and specific (100%) for both c-MET-negative cells and in 20 HVs. Of 52 patients with metastatic carcinomas tested, c-MET CTCs were captured in replicate samples from 3 patients [gastric, colorectal, and renal cell carcinoma (RCC)] with 6% prevalence. CTC FISH demonstrated that MET amplification in both gastric and colorectal cancer patients and trisomy 7 with gain of MET gene copies in the RCC patient. The c-MET CTC assay is a rapid, noninvasive, sensitive, and specific method for detecting MET-amplified tumor cells. CTCs with MET amplification can be detected in patients with gastric, colorectal, and renal cancers. Implications: This study developed a novel c-MET CTC assay for detecting c-MET CTCs in patients with MET amplification and warrants further investigation to determine its clinical applicability.

Original languageEnglish (US)
Pages (from-to)539-547
Number of pages9
JournalMolecular Cancer Research
Volume14
Issue number6
DOIs
StatePublished - Jun 1 2016
Externally publishedYes

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ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Oncology

Cite this

Zhang, T., Boominathan, R., Foulk, B., Rao, C., Kemeny, G., Strickler, J. H., Abbruzzese, J. L., Harrison, M. R., Hsu, D. S., Healy, P., Li, J., Pi, C., Prendergast, K. M., Hobbs, C., Gemberling, S., George, D. J., Hurwitz, H. I., Connelly, M., Garcia-Blanco, M., & Armstrong, A. J. (2016). Development of a novel c-MET-Based CTC detection platform. Molecular Cancer Research, 14(6), 539-547. https://doi.org/10.1158/1541-7786.MCR-16-0011