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. 2022 May 14;14(10):2433.
doi: 10.3390/cancers14102433.

MET Expression Level in Lung Adenocarcinoma Loosely Correlates with MET Copy Number Gain/Amplification and Is a Poor Predictor of Patient Outcome

Wei Yin  1   2 , Ming Guo  3 , Zhenya Tang  1 , Gokce A Toruner  1 , Joanne Cheng  1 , L Jeffrey Medeiros  1 , Guilin Tang  1
Affiliations

MET Expression Level in Lung Adenocarcinoma Loosely Correlates with MET Copy Number Gain/Amplification and Is a Poor Predictor of Patient Outcome

Wei Yin et al. Cancers (Basel). .

Abstract

MET amplification has been associated with shorter survival in cancer patients, however, the potential correlation of MET overexpression with either MET amplification or patient outcome is controversial. The aim of this study was to address these questions by correlating MET expression level with MET copy number and patient outcome in a cohort of 446 patients who had a lung adenocarcinoma: 88 with MET amplification, 118 with polysomy 7, and 240 with negative results by fluorescence in situ hybridization. MET expression assessed by immunohistochemistry was semi-quantified by expression level: absent (0+), weak (1+), moderate (2+) and strong (3+); or by H-score: 0-99, 100-199, and ≥200. MET expression level or H-score was positively but weakly correlated with MET copy number or MET/CEP7 ratio. Strong expression of MET (3+ or H-score ≥ 200) was associated with a shorter overall survival, but it was not an independent hazard for survival by multivariant analysis. We conclude that MET expression is loosely correlated with MET copy number gain/amplification. Strong expression of MET does not independently predict patient outcome.

Keywords: MET amplification; MET expression; lung cancer; survival.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Fluorescence in situ hybridization (FISH) analysis using MET/CEP7 probes (×60). (A): MET negative; (B): Polysomy 7 (copy number gain detected in both MET and CEP7); (C): MET amplification (copy number gain in MET, not in CEP7, MET/CEP7 ratio > 1.8); (D): MET amplification (clusters of MET signals). FISH probe signals: MET in red and centromere 7 (CEP7) in green.
Figure 2
Figure 2
MET expression level by immunohistochemistry stain (×20). (A): Absent (0+); (B): Weak (1+); (C): Moderate (2+); (D): Strong (3+).
Figure 3
Figure 3
Correlation of FISH groups and immunohistochemistry results. (A): Proportion of patients with different level of MET expression (IHC0+~3+) in patients with MET-amp, Polysomy 7 and MET-neg. (B): Proportion of patients with MET H-score of 0–99, 100–199 and ≥200 in patients with MET amp, Polysomy 7 and MET neg. Presented as percentage of cases.
Figure 4
Figure 4
Overall survival (OS) by Kaplan-Meier analysis. (A): Comparison of OS among patients with MET-amp, polysomy 7 and MET-neg, patients in MET-amp group showed significantly inferior OS; (B): No significant difference of OS among patients of groups with of IHC-neg, IHC1+, IGHC2+ and IHC3+; (C): Patients with IHC3+ showed a significantly shorter OS comparing to patients with IHC0/1+/2+; (D): Patients with H- score ≥ 200 showed a significantly inferior OS comparing to patients with H score < 200.
See this image and copyright information in PMC

References

    1. Birchmeier C., Birchmeier W., Gherardi E., Vande Woude G.F. Met, metastasis, motility and more. Nat. Rev. Mol. Cell. Biol. 2003;4:915–925. doi: 10.1038/nrm1261. - DOI - PubMed
    1. Frampton G.M., Ali S.M., Rosenzweig M., Chmielecki J., Lu X., Bauer T.M., Akimov M., Bufill J.A., Lee C., Jentz D., et al. Activation of MET via diverse exon 14 splicing alterations occurs in multiple tumor types and confers clinical sensitivity to MET inhibitors. Cancer Discov. 2015;5:850–859. doi: 10.1158/2159-8290.CD-15-0285. - DOI - PubMed
    1. Drilon A., Cappuzzo F., Ou S.I., Camidge D.R. Targeting MET in Lung Cancer: Will Expectations Finally Be MET? J. Thorac. Oncol. 2017;12:15–26. doi: 10.1016/j.jtho.2016.10.014. - DOI - PMC - PubMed
    1. Dagogo-Jack I., Yoda S., Lennerz J.K., Langenbucher A., Lin J.J., Rooney M.M., Prutisto-Chang K., Oh A., Adams N.A., Yeap B.Y., et al. MET Alterations Are a Recurring and Actionable Resistance Mechanism in ALK-Positive Lung Cancer. Clin. Cancer Res. 2020;26:2535–2545. doi: 10.1158/1078-0432.CCR-19-3906. - DOI - PMC - PubMed
    1. Wu Y.L., Zhang L., Kim D.W., Liu X., Lee D.H., Yang J.C., Ahn M.J., Vansteenkiste J.F., Su W.C., Felip E., et al. Phase Ib/II Study of Capmatinib (INC280) Plus Gefitinib After Failure of Epidermal Growth Factor Receptor (EGFR) Inhibitor Therapy in Patients With EGFR-Mutated, MET Factor-Dysregulated Non-Small-Cell Lung Cancer. J. Clin. Oncol. 2018;36:3101–3109. doi: 10.1200/JCO.2018.77.7326. - DOI - PubMed

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