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FISH, MET Amplification

Test code(s) 91283

Question 1. What is the role of MET in lung cancer?

The MET protein is a receptor kinase that stimulates tyrosine-kinase activity, as does EGFR. Stimulated tyrosine kinase leads to activation of signaling pathways associated with cell growth and survival. Thus, MET protein overexpression, MET proto-oncogene amplification, and MET exon 14 skipping mutation lead to tumor growth and progression and unfavorable prognosis in patients with non-small-cell lung cancer (NSCLC).

MET amplification is associated with acquired resistance to EGFR tyrosine kinase inhibitor (TKI) therapy in patients with NSCLC and EGFR-activating mutations. Crizotinib (see NCCN guidelines) or other MET-targeted treatment may be considered in NSCLC cases with high-level MET amplification or MET exon 14 skipping mutation.1

Question 2. How do MET-activating mutations correlate with other mutations seen in lung cancer?

MET mutations may coexist with other oncogene mutations (eg, KRAS, EGFR, BRAF, ALK). Similar to mutations in these other oncogenes, MET overexpression and/or amplification is associated with a more aggressive disease.

Question 3. How does the FISH MET Amplification assay work?

The MET (7q31) FISH dual-color probe set is hybridized with a control probe (D7Z1) to evaluate copy number gain in interphase cells from the lesion of interest.

Question 4. What is the significance of the different patterns of increased MET signals, and how is the assay scored?

Normal tissues should have an average of two MET signals and two control probe (D7Z1) signals. The over-representation of MET compared to the control is an indicator of copy number gain.

The scoring system is a combination of MET copy number per cell, MET/ D7Z1 ratio and percentage (%) of cells positive.

Question 5. Which specimens can be tested?

Formalin-fixed, paraffin-embedded tissue and fresh tumor tissue can be tested.

Question 6. How does the MET FISH assay compare to the MET-phospho IHC?

The FISH assay determines the gene copy number (ie, MET amplification), while the IHC assay determines the level of gene expression (ie, MET overexpression). Although FISH and IHC results usually correlate with each other, NCCN guidelines recommends FISH testing only for MET amplification.

Question 7. What is the most common alias for MET?

The most common alias is c-MET.

Question 8. Are there therapeutic agents that can be used to treat NSCLCs with MET amplification?

Possibly. The NCCN guidelines consider crizotinib an emerging therapy for NSCLCs with a high-level MET amplification or MET exon 14 skipping mutation.1 Additional MET inhibitors are under investigation.

Reference

  1. NCCN Clinical Practice Guidelines in Oncology. Non-small cell lung cancer: NCCN Evidence Blocks™, V3.2017. NCCN.org/professionals/physician_gls/pdf/nscl_blocks.pdf. Published November 16, 2016. Accessed December 19, 2016.
This FAQ is provided for informational purposes only and is not intended as medical advice. A physician’s test selection and interpretation, diagnosis, and patient management decisions should be based on his/her education, clinical expertise, and assessment of the patient.
Document FAQS.84 Version: 1
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Version 0 effective 10/15/2012 to 02/06/2017