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Evaluation of a novel c-MET based circulating tumor cell (CTC) biomarker in patients with gastrointestinal malignancies.

Publication ,  Conference
Zhang, T; Boominathan, R; Foulk, B; Connelly, MC; Rao, C; Kemeny, G; Hurwitz, H; Garcia-Blanco, MA; Armstrong, AJ
Published in: Journal of Clinical Oncology
January 20, 2015

84 Background: Multiple GI malignancies including gastric, pancreatic, and colorectal cancers harbor genetic alterations in the MET oncogene. MET amplification is associated with poor prognosis, and c-MET targeted therapies are in development. We aimed to capture and identify c-MET CTCs using a non-invasive, rapid test. Methods: We modified the CELLSEARCH platform by using nanomagnetic particles conjugated to antibodies against the extracellular domain of c-MET to capture c-MET-expressing CTCs. The method was validated by spiking MET-amplified gastric cancer cells, c-MET-overexpressing, nonamplified cancer cells, and MET-negative cancer cells into peripheral blood from healthy volunteers. Peripheral blood samples were obtained from patients (pts) with refractory metastatic gastric, pancreatic, and colorectal cancers, prepared in duplicate, and characterized by immunofluorescence staining for intracellular c-MET-PE, DAPI, and pan-CK-FITC. CD45 + cells were excluded. CTC enumeration with c-MET capture was compared to EpCAM capture. After CTC isolation, MET DNA FISH was performed. Results: The novel c-MET CTC assay was found to be 80% sensitive for MET-amplified cells, 40-80% sensitive for c-MET-overexpressed cells, and 100% specific for c-MET negative cells and in 10 healthy volunteers. In 7/7 pts with metastatic pancreatic and 8/8 pts with metastatic colorectal cancers, we did not capture c-MET CTCs. Of 3 gastric cancer pts tested thus far, one pt had a significant number of c-MET + CTCs, with 52 CTCs and 90 CTCs in each of the duplicate samples, compared to 20 CTCs with EpCAM capture. CTC FISH demonstrated polysomy 7 and METamplification. This pt had HER2 amplification in primary tumor tissue and had progressed on FOLFOX and trastuzumab at the time of enrollment. Conclusions: We have developed a sensitive and specific c-MET CTC assay. c-MET-expressing CTCs can be detected in gastric cancer but not controls or other GI cancers to date. While not detectable in many pts, high levels in one pt support the importance of MET amplification as a resistance mechanism to HER2 therapy, and suggest that this approach may be useful to identify and follow patients who may be candidates for c-MET directed therapies.

Duke Scholars

Published In

Journal of Clinical Oncology

DOI

EISSN

1527-7755

ISSN

0732-183X

Publication Date

January 20, 2015

Volume

33

Issue

3_suppl

Start / End Page

84 / 84

Publisher

American Society of Clinical Oncology (ASCO)

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis
  • 1103 Clinical Sciences
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Zhang, T., Boominathan, R., Foulk, B., Connelly, M. C., Rao, C., Kemeny, G., … Armstrong, A. J. (2015). Evaluation of a novel c-MET based circulating tumor cell (CTC) biomarker in patients with gastrointestinal malignancies. In Journal of Clinical Oncology (Vol. 33, pp. 84–84). American Society of Clinical Oncology (ASCO). https://doi.org/10.1200/jco.2015.33.3_suppl.84
Zhang, Tian, Rengasamy Boominathan, Brad Foulk, Mark Carle Connelly, Chandra Rao, Gabor Kemeny, Herbert Hurwitz, Mariano A. Garcia-Blanco, and Andrew J. Armstrong. “Evaluation of a novel c-MET based circulating tumor cell (CTC) biomarker in patients with gastrointestinal malignancies.” In Journal of Clinical Oncology, 33:84–84. American Society of Clinical Oncology (ASCO), 2015. https://doi.org/10.1200/jco.2015.33.3_suppl.84.
Zhang T, Boominathan R, Foulk B, Connelly MC, Rao C, Kemeny G, et al. Evaluation of a novel c-MET based circulating tumor cell (CTC) biomarker in patients with gastrointestinal malignancies. In: Journal of Clinical Oncology. American Society of Clinical Oncology (ASCO); 2015. p. 84–84.
Zhang, Tian, et al. “Evaluation of a novel c-MET based circulating tumor cell (CTC) biomarker in patients with gastrointestinal malignancies.Journal of Clinical Oncology, vol. 33, no. 3_suppl, American Society of Clinical Oncology (ASCO), 2015, pp. 84–84. Crossref, doi:10.1200/jco.2015.33.3_suppl.84.
Zhang T, Boominathan R, Foulk B, Connelly MC, Rao C, Kemeny G, Hurwitz H, Garcia-Blanco MA, Armstrong AJ. Evaluation of a novel c-MET based circulating tumor cell (CTC) biomarker in patients with gastrointestinal malignancies. Journal of Clinical Oncology. American Society of Clinical Oncology (ASCO); 2015. p. 84–84.

Published In

Journal of Clinical Oncology

DOI

EISSN

1527-7755

ISSN

0732-183X

Publication Date

January 20, 2015

Volume

33

Issue

3_suppl

Start / End Page

84 / 84

Publisher

American Society of Clinical Oncology (ASCO)

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis
  • 1103 Clinical Sciences