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Matikas A, Voutsina A, Lagoudaki E, et al. Detection of KRAS Exon 2 Mutations in Circulating Tumor Cells Isolated by the ISET System from Patients with RAS Wild Type Metastatic Colorectal Cancer. Transl Oncol. 2017;10(4):693-698doi: 10.1016/j.tranon.2017.06.005.
Matikas, A., Voutsina, A., Lagoudaki, E., Hatzidaki, D., Trypaki, M., Stoupis, G., Tzardi, M., Mavroudis, D., & Georgoulias, V. (2017). Detection of KRAS Exon 2 Mutations in Circulating Tumor Cells Isolated by the ISET System from Patients with RAS Wild Type Metastatic Colorectal Cancer. Translational oncology, 10(4), 693-698. https://doi.org/10.1016/j.tranon.2017.06.005
Matikas, Alexios, et al. "Detection of KRAS Exon 2 Mutations in Circulating Tumor Cells Isolated by the ISET System from Patients with RAS Wild Type Metastatic Colorectal Cancer." Translational oncology vol. 10,4 (2017): 693-698. doi: https://doi.org/10.1016/j.tranon.2017.06.005
Matikas A, Voutsina A, Lagoudaki E, Hatzidaki D, Trypaki M, Stoupis G, Tzardi M, Mavroudis D, Georgoulias V. Detection of KRAS Exon 2 Mutations in Circulating Tumor Cells Isolated by the ISET System from Patients with RAS Wild Type Metastatic Colorectal Cancer. Transl Oncol. 2017 Aug;10(4):693-698. doi: 10.1016/j.tranon.2017.06.005. Epub 2017 Jul 07. PMID: 28692881; PMCID: PMC5503828.
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Transl Oncol. 2017 Aug;10(4):693-698. doi: 10.1016/j.tranon.2017.06.005. Epub 2017 Jul 07.

Detection of KRAS Exon 2 Mutations in Circulating Tumor Cells Isolated by the ISET System from Patients with RAS Wild Type Metastatic Colorectal Cancer.

Translational oncology

Alexios Matikas, Alexandra Voutsina, Eleni Lagoudaki, Dora Hatzidaki, Maria Trypaki, Giannis Stoupis, Maria Tzardi, Dimitrios Mavroudis, Vasilios Georgoulias

Affiliations

  1. Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden; Department of Medical Oncology, University Hospital of Heraklion, Greece. Electronic address: [email protected].
  2. Laboratory of Translational Oncology, School of Medicine, University of Crete, Heraklion, Greece.
  3. Department of Pathology, University Hospital of Heraklion, Greece.
  4. Department of Medical Oncology, University Hospital of Heraklion, Greece.
  5. Laboratory of Translational Oncology, School of Medicine, University of Crete, Heraklion, Greece; Department of Medical Oncology, University Hospital of Heraklion, Greece.
  6. School of Medicine, University of Crete, Heraklion, Greece.

PMID: 28692881 PMCID: PMC5503828 DOI: 10.1016/j.tranon.2017.06.005

Abstract

INTRODUCTION: The presence of KRAS mutations in patients with metastatic colorectal cancer (mCRC) predicts poor response to agents targeting the EGFR. Even in patients with RAS wild type (WT) tumors, resistance eventually develops due to multiple mechanisms, including the expansion of previously undetected KRAS mutated clones. In this feasibility study, we aimed to detect KRAS exon 2 mutations in serial samples of circulating tumor cells (CTCs) of RAS WT patients with mCRC captured by the Isolation by Size of Epithelial Tumor cells (ISET) system.

METHODS: CTC isolation using the ISET system was performed from prospectively collected blood samples obtained from patients with RAS and BRAF WT mCRC prior to first-line therapy initiation, at first imaging assessment and on disease progression. CTCs were enumerated using hematoxylin & eosin and CD45 double stain on a single membrane spot. DNA was extracted from 5 spots and KRAS exon 2 mutations were detected using a custom quantitative Polymerase Chain Reaction (qPCR) assay.

RESULTS: Fifteen patients were enrolled and 28 blood samples were analyzed. In 9 (60%) patients, at least one sample was positive for the presence of a KRAS exon 2 mutation. In 11 out of 28 samples (39.2%) with detectable CTCs a KRAS mutation was detected; the corresponding percentages for baseline and on progression samples were 27% and 37.5%, respectively. The most commonly detected mutations were G13D and G12C (n=3). The presence of KRAS mutated CTCs at baseline was not prognostic for either PFS (P=.950) or OS (P=.383). CTC kinetics did not follow tumor response patterns.

CONCLUSION: The results demonstrate that using a qPCR-based assay, KRAS exon 2 mutations could be detected in CTCs captured by the ISET system from patients with RAS WT primary tumors. However, the clinical relevance of these CTCs remains to be determined in future studies.

Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

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