Discover MET in NSCLC

The MET pathway is dysregulated in NSCLC1,2
MET/c-Met overexpression, MET gene amplification, and METex14 skipping mutations contribute to disease pathogenesis and are associated with poor prognosis
c-Met overexpression is the most prevalent MET aberration3,4
c-Met overexpression is an emerging biomarker in NSCLC, with ~25% prevalence in EGFR wild-type non-squamous NSCLC compared to ~2–4% for METex14 skipping mutations and ~2–5% for MET gene amplification
c-Met overexpression is an emerging biomarker and requires IHC analysis5,6*
IHC is an established testing modality in NSCLC. NGS and FISH are molecular tests and cannot be used to detect protein expression
*Not all methods shown here are FDA-approved for MET testing. There are no FDA-approved tests for c-Met overexpression or MET gene amplification7
EGFR=epidermal growth factor receptor; FISH=fluorescence in situ hybridization;
IHC=immunohistochemistry; MET=mesenchymal-epithelial transition;
NGS=next-generation sequencing; NSCLC=non-small cell lung cancer.
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Discover MET in NSCLC

The MET pathway is dysregulated in NSCLC1,2
MET/c-Met overexpression, MET gene amplification, and METex14 skipping mutations contribute to disease pathogenesis and are associated with poor prognosis
c-Met overexpression is the most prevalent MET aberration3,4
c-Met overexpression is an emerging biomarker in NSCLC, with ~25% prevalence in EGFR wild-type non-squamous NSCLC compared to ~2–4% for METex14 skipping mutations and ~2–5% for MET gene amplification
c-Met overexpression is an emerging biomarker and requires IHC analysis5,6*
IHC is an established testing modality in NSCLC. NGS and FISH are molecular tests and cannot be used to detect protein expression
*Not all methods shown here are FDA-approved for MET testing. There are no FDA-approved tests for c-Met overexpression or MET gene amplification7
EGFR=epidermal growth factor receptor; FISH=fluorescence in situ hybridization; IHC=immunohistochemistry; MET=mesenchymal-epithelial transition; NGS=next-generation sequencing; NSCLC=non-small cell lung cancer.
Down arrow

Discover MET in NSCLC

The MET pathway is dysregulated in NSCLC1,2
MET/c-Met overexpression, MET gene amplification, and METex14 skipping mutations contribute to disease pathogenesis and are associated with poor prognosis
c-Met overexpression is the most prevalent MET aberration3,4
c-Met overexpression is an emerging biomarker in NSCLC, with ~25% prevalence in EGFR wild-type non-squamous NSCLC compared to ~2–4% for METex14 skipping mutations and ~2–5% for MET gene amplification
c-Met overexpression is an emerging biomarker and requires IHC analysis5,6*
IHC is an established testing modality in NSCLC. NGS and FISH are molecular tests and cannot be used to detect protein expression
*Not all methods shown here are FDA-approved for MET testing. There are no FDA-approved tests for c-Met overexpression or MET gene amplification7
EGFR=epidermal growth factor receptor; FISH=fluorescence in situ hybridization; IHC=immunohistochemistry; MET=mesenchymal-epithelial transition; NGS=next-generation sequencing; NSCLC=non-small cell lung cancer.
Down arrow

MET signaling in NSCLC is dysregulated through mechanisms including, but not limited to, c-Met overexpression, MET gene amplification, METex14 skipping mutations and HGF overexpression.* MET aberrations are associated with poor prognosis in NSCLC4–7

MET Aberrations in NSCLC
*Not all MET aberrations have FDA-approved CDx for NSCLC7
†EGFR wild-type non-squamous NSCLC. ‡Intermediate expression: ≥25 to <50% of tumor cells with strong membrane and/or cytoplasmic staining at 3+ intensity using the SP44 anti–c-Met antibody. High expression: ≥50% of tumor cells with strong membrane and/or cytoplasmic staining at 3+ intensity using the SP44 anti–c-Met antibody.8
CDx=companion diagnostic; EGFR=epidermal growth factor receptor; HGF=hepatocyte growth factor; MET=mesenchymal-epithelial transition; mRNA=messenger RNA; NSCLC=non-small cell lung cancer.
c-Met Overexpression
*Not all MET aberrations have FDA-approved CDx for NSCLC7
†EGFR wild-type non-squamous NSCLC. ‡Intermediate expression: ≥25 to <50% of tumor cells with strong membrane and/or cytoplasmic staining at 3+ intensity using the SP44 anti–c-Met antibody. High expression: ≥50% of tumor cells with strong membrane and/or cytoplasmic staining at 3+ intensity using the SP44 anti–c-Met antibody.8 §Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.3.2023. © National Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed August 10, 2023. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
CDx=companion diagnostic; EGFR=epidermal growth factor receptor; HGF=hepatocyte growth factor; MET=mesenchymal-epithelial transition; mRNA=messenger RNA; NCCN=National Comprehensive Cancer Network; NSCLC=non-small cell lung cancer.
METex14 Skipping Mutations
*Not all MET aberrations have FDA-approved CDx for NSCLC7
†EGFR wild-type non-squamous NSCLC. ‡Intermediate expression: ≥25 to <50% of tumor cells with strong membrane and/or cytoplasmic staining at 3+ intensity using the SP44 anti–c-Met antibody. High expression: ≥50% of tumor cells with strong membrane and/or cytoplasmic staining at 3+ intensity using the SP44 anti–c-Met antibody.8 §Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.3.2023. © National Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed August 10, 2023. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
CDx=companion diagnostic; EGFR=epidermal growth factor receptor; FDA=Food and Drug Administration; HGF=hepatocyte growth factor; MET=mesenchymal-epithelial transition; mRNA=messenger RNA; NCCN=National Comprehensive Cancer Network; NSCLC=non-small cell lung cancer.
MET Gene Amplification
*Not all MET aberrations have FDA-approved CDx for NSCLC7
†EGFR wild-type non-squamous NSCLC. ‡Intermediate expression: ≥25 to <50% of tumor cells with strong membrane and/or cytoplasmic staining at 3+ intensity using the SP44 anti–c-Met antibody. High expression: ≥50% of tumor cells with strong membrane and/or cytoplasmic staining at 3+ intensity using the SP44 anti–c-Met antibody.8 §Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.3.2023. © National Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed August 10, 2023. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. ||The definition of high-level MET amplification is evolving and may differ according to the assay used for testing. For NGS-based results, a copy number greater than 10 is consistent with high-level MET amplification.
CDx=companion diagnostic; EGFR=epidermal growth factor receptor; MET=mesenchymal-epithelial transition; FDA=Food and Drug Administration; HGF=hepatocyte growth factor; mRNA=messenger RNA; NCCN=National Comprehensive Cancer Network; NGS=next-generation sequencing; NSCLC=non-small cell lung cancer.
MET Aberrations in NSCLC
*Not all MET aberrations have FDA-approved CDx for NSCLC7
†EGFR wild-type non-squamous NSCLC. ‡Intermediate expression: ≥25 to <50% of tumor cells with strong membrane and/or cytoplasmic staining at 3+ intensity using the SP44 anti–c-Met antibody. High expression: ≥50% of tumor cells with strong membrane and/or cytoplasmic staining at 3+ intensity using the SP44 anti–c-Met antibody.8
CDx=companion diagnostic; EGFR=epidermal growth factor receptor; HGF=hepatocyte growth factor; MET=mesenchymal-epithelial transition; mRNA=messenger RNA; NSCLC=non-small cell lung cancer.
c-Met Overexpression
*Not all MET aberrations have FDA-approved CDx for NSCLC7
†EGFR wild-type non-squamous NSCLC. ‡Intermediate expression: ≥25 to <50% of tumor cells with strong membrane and/or cytoplasmic staining at 3+ intensity using the SP44 anti–c-Met antibody. High expression: ≥50% of tumor cells with strong membrane and/or cytoplasmic staining at 3+ intensity using the SP44 anti–c-Met antibody.8 §Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.3.2023. © National Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed August 10, 2023. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
CDx=companion diagnostic; EGFR=epidermal growth factor receptor; HGF=hepatocyte growth factor; MET=mesenchymal-epithelial transition; mRNA=messenger RNA; NCCN=National Comprehensive Cancer Network; NSCLC=non-small cell lung cancer.
METex14 Skipping Mutations
*Not all MET aberrations have FDA-approved CDx for NSCLC7
†EGFR wild-type non-squamous NSCLC. ‡Intermediate expression: ≥25 to <50% of tumor cells with strong membrane and/or cytoplasmic staining at 3+ intensity using the SP44 anti–c-Met antibody. High expression: ≥50% of tumor cells with strong membrane and/or cytoplasmic staining at 3+ intensity using the SP44 anti–c-Met antibody.8 §Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.3.2023. © National Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed August 10, 2023. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
CDx=companion diagnostic; EGFR=epidermal growth factor receptor; FDA=Food and Drug Administration; HGF=hepatocyte growth factor; MET=mesenchymal-epithelial transition; mRNA=messenger RNA; NCCN=National Comprehensive Cancer Network; NSCLC=non-small cell lung cancer.
MET Gene Amplification
*Not all MET aberrations have FDA-approved CDx for NSCLC7
†EGFR wild-type non-squamous NSCLC. ‡Intermediate expression: ≥25 to <50% of tumor cells with strong membrane and/or cytoplasmic staining at 3+ intensity using the SP44 anti–c-Met antibody. High expression: ≥50% of tumor cells with strong membrane and/or cytoplasmic staining at 3+ intensity using the SP44 anti–c-Met antibody.8 §Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.3.2023. © National Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed August 10, 2023. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. ||The definition of high-level MET amplification is evolving and may differ according to the assay used for testing. For NGS-based results, a copy number greater than 10 is consistent with high-level MET amplification.
CDx=companion diagnostic; EGFR=epidermal growth factor receptor; MET=mesenchymal-epithelial transition; FDA=Food and Drug Administration; HGF=hepatocyte growth factor; mRNA=messenger RNA; NCCN=National Comprehensive Cancer Network; NGS=next-generation sequencing; NSCLC=non-small cell lung cancer.
MET Aberrations in NSCLC

c-Met overexpression is the most prevalent MET aberration relative to METex14 skipping mutations and MET gene amplification.3,4

c-Met overexpression is an emerging biomarker in advanced NSCLC.3,8*

*Not all MET aberrations have FDA-approved CDx for NSCLC7
†EGFR wild-type non-squamous NSCLC. ‡Intermediate expression: ≥25 to <50% of tumor cells with strong membrane and/or cytoplasmic staining at 3+ intensity using the SP44 anti–c-Met antibody. High expression: ≥50% of tumor cells with strong membrane and/or cytoplasmic staining at 3+ intensity using the SP44 anti–c-Met antibody.8
CDx=companion diagnostic; EGFR=epidermal growth factor receptor; HGF=hepatocyte growth factor; MET=mesenchymal-epithelial transition; mRNA=messenger RNA; NSCLC=non-small cell lung cancer.
c-Met Overexpression
c-Met Overexpression
Cause4,9
Changes in epigenetic, transcriptional, and post-transcriptional regulation
Role as a Biomarker3,8*
Emerging biomarker
Associated Therapies3,8
Target under clinical development
Testing Guidelines10§
Not yet included among National Comprehensive Cancer Network® (NCCN®) recommended biomarkers
*Not all MET aberrations have FDA-approved CDx for NSCLC7
†EGFR wild-type non-squamous NSCLC. ‡Intermediate expression: ≥25 to <50% of tumor cells with strong membrane and/or cytoplasmic staining at 3+ intensity using the SP44 anti–c-Met antibody. High expression: ≥50% of tumor cells with strong membrane and/or cytoplasmic staining at 3+ intensity using the SP44 anti–c-Met antibody.8 §Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.3.2023. © National Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed August 10, 2023. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
CDx=companion diagnostic; EGFR=epidermal growth factor receptor; HGF=hepatocyte growth factor; MET=mesenchymal-epithelial transition; mRNA=messenger RNA; NCCN=National Comprehensive Cancer Network; NSCLC=non-small cell lung cancer.
METex14 Skipping Mutations
METex14 Skipping Mutations
Cause3,8
Disruption in mRNA splicing, resulting in the loss of a key regulatory domain and impaired c-Met degradation
Role as a Biomarker7,11*
FDA-approved CDx in NSCLC
Associated Therapies7,10§
Small molecule tyrosine kinase inhibitors
Testing Guidelines10§
Testing recommended in advanced or metastatic disease to identify patients for targeted agents
*Not all MET aberrations have FDA-approved CDx for NSCLC7
†EGFR wild-type non-squamous NSCLC. ‡Intermediate expression: ≥25 to <50% of tumor cells with strong membrane and/or cytoplasmic staining at 3+ intensity using the SP44 anti–c-Met antibody. High expression: ≥50% of tumor cells with strong membrane and/or cytoplasmic staining at 3+ intensity using the SP44 anti–c-Met antibody.8 §Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.3.2023. © National Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed August 10, 2023. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
CDx=companion diagnostic; EGFR=epidermal growth factor receptor; FDA=Food and Drug Administration; HGF=hepatocyte growth factor; MET=mesenchymal-epithelial transition; mRNA=messenger RNA; NCCN=National Comprehensive Cancer Network; NSCLC=non-small cell lung cancer.
MET Gene Amplification
MET Gene Amplification
Cause3,8
Increase in the number of copies of the MET gene
Role as a Biomarker10*§
Emerging biomarker
Associated Therapies7,10§
No FDA-approved therapies currently available
Testing Guidelines10§
High-level MET amplification|| is an emerging biomarker to identify novel therapies for patients with metastatic NSCLC
*Not all MET aberrations have FDA-approved CDx for NSCLC7
†EGFR wild-type non-squamous NSCLC. ‡Intermediate expression: ≥25 to <50% of tumor cells with strong membrane and/or cytoplasmic staining at 3+ intensity using the SP44 anti–c-Met antibody. High expression: ≥50% of tumor cells with strong membrane and/or cytoplasmic staining at 3+ intensity using the SP44 anti–c-Met antibody.8 §Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.3.2023. © National Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed August 10, 2023. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. ||The definition of high-level MET amplification is evolving and may differ according to the assay used for testing. For NGS-based results, a copy number greater than 10 is consistent with high-level MET amplification.
CDx=companion diagnostic; EGFR=epidermal growth factor receptor; MET=mesenchymal-epithelial transition; FDA=Food and Drug Administration; HGF=hepatocyte growth factor; mRNA=messenger RNA; NCCN=National Comprehensive Cancer Network; NGS=next-generation sequencing; NSCLC=non-small cell lung cancer.

Due to their role in carcinogenesis and cancer progression, MET aberrations are emerging as biomarkers in NSCLC1,4,8

Learn more about the methods
used to test for MET aberrations
Arrows
References
  1. Guo B, Cen H, Tan X, Liu W, Ke Q. Prognostic value of MET gene copy number and protein expression in patients with surgically resected non-small cell lung cancer: a meta-analysis of published literatures. PLoS One. 2014;9(6):e99399. doi:10.1371/journal.pone.0099399
  2. Lee GD, Lee SE, Oh DY, et al. MET exon 14 skipping mutations in lung adenocarcinoma: Clinicopathologic implications and prognostic values. J Thorac Oncol. 2017;12(8):1233-1246. doi:10.1016/j.jtho.2017.04.031
  3. Motwani M, Panchabhai S, Bar J, et al. P60.12 Prevalence of c-Met overexpression (c-Met+) and impact of prior lines of treatment on c-Met protein expression in NSCLC. JTO. 2021;16(10):S1169-S1170. doi:10.1016/j. jtho.2021.08.633
  4. Liang H, Wang M. MET oncogene in non-small cell lung cancer: mechanism of MET dysregulation and agents targeting the HGF/c-Met axis. Onco Targets Ther. 2020;13:2491-2510. doi:10.2147/OTT.S231257
  5. Park S, Choi YL, Sung CO, et al. High MET copy number and MET overexpression: poor outcome in non-small cell lung cancer patients. Histol Histopathol. 2012;27(2):197-207. doi:10.14670/HH-27.197
  6. Sun W, Song L, Ai T, et al. Prognostic value of MET, cyclin D1 and MET gene copy number in non-small cell lung cancer. J Biomed Res. 2013;27(3):220-230. doi:10.7555/JBR.27.20130004
  7. List of cleared or approved companion diagnostic devices. US Food and Drug Administration. Updated August 21, 2023. Accessed August 22, 2023. https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools
  8. Ansell PJ, Bailjal S, Liede A, et al. Prevalence and characterization of c-Met-overexpressing non-small cell lung cancer (NSCLC) across clinical trial samples and real-world patient cohorts from the City of Hope National Medical Center. Paper presented at: CRUK Lung Cancer Conference; Nov 15–17, 2022; Manchester, UK.
  9. Gherardi E, Birchmeier W, Birchmeier C, Vande Woude G. Targeting MET in cancer: Rationale and progress. Nat Rev Cancer. 2012;12(2):89-103. doi:10.1038/nrc3205
  10. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.3.2023. © National Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed August 10, 2023. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
  11. Zhang YL, Yuan JQ, Wang KF, et al. The prevalence of EGFR mutation in patients with non-small cell lung cancer: a systematic review and meta-analysis. Oncotarget. 2016;7(48):78985-78993. doi:10.18632/oncotarget.12587
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