Mesenchyme to epithelial transition protein expression, gene copy number and clinical outcome in a large non-small cell lung cancer surgical cohort

Gareth Rivalland*, Paul Mitchell, Carmel Murone, Khashayer Asadi, Adrienne L. Morey, Maud Starmans, Paul C. Boutros, Marzena Walkiewicz, Benjamin Solomon, Gavin Wright, Simon Knight, Thomas John

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

4 Citations (Web of Science)

Abstract

Background: In non-small cell lung cancer (NSCLC), mesenchyme to epithelial transition (MET) protein abundance increases with disease stage and is implicated in resistance to tyrosine kinase inhibitors. To better clarify the impact of MET overexpression on tumor behavior, we investigated a large cohort of patients who underwent curative surgical resection to determine whether MET gene amplification or protein abundance was prognostic.

Methods: Tissue microarrays (TMAs) were constructed using triplicate 1 mm cores of FFPE primary NSCLC specimens. TMAs underwent immunohistochemical (IHC) staining with the SP44 clone (Ventana) and cores were considered positive if >50% of tumor exhibited 2+ staining. The highest of triplicate values was used. MET gene amplification was detected using either SISH using Ventana's MET DNP probe or FISH using the D7S486/CEP 7 Abbott Probe. DNA was subjected to mutational profiling using Sequenom's LungCarta panel.

Results: Data from two institutions comprising 763 patients (516; 68%) male were generated, including 360 stage I, 226 stage II, 160 stage III and 18 resected stage IV. High MET protein expression was detected in 25% (193/763), and was significantly more common in adenocarcinomas than squamous cell carcinoma (P

Conclusions: MET expression by IHC and GCN amplification was not prognostic in this large Caucasian surgical series. MET's primary role remains as a therapeutic target.

Original languageEnglish
Pages (from-to)167-175
Number of pages9
JournalTranslational Lung Cancer Research
Volume8
Issue number2
DOIs
Publication statusPublished - Apr 2019

Keywords

  • Immunohistochemistry
  • in situ hybridisation
  • mesenchyme to epithelial transition receptor (MET receptor)
  • mesenchyme to epithelial transition amplification (MET amplification)
  • non-small cell lung cancer (NSCLC)
  • PHASE-II TRIAL
  • PROGNOSTIC VALUE
  • MET
  • ERLOTINIB
  • ONARTUZUMAB
  • ACTIVATION
  • MUTATIONS
  • TARGET

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