Alterations of MET Gene Copy Number and Protein Expression in Primary Non-Small-Cell Lung Cancer and Corresponding Nodal Metastases.

Tran, TN; Selinger, CI; Kohonen-Corish, MRJ; McCaughan, B; Kennedy, C; O'Toole, SA; Cooper, WA

Alterations of MET Gene Copy Number and Protein Expression in Primary Non-Small-Cell Lung Cancer and Corresponding Nodal Metastases.

Tran, TN Selinger, CI Kohonen-Corish, MRJ McCaughan, B Kennedy, C O'Toole, SA Cooper, WA

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Publisher:: CIG MEDIA GROUP, LP
Publication Type:: Journal Article
Citation:: Clin Lung Cancer, 2016, 17, (1), pp. 30-8.e1
Issue Date:: 2016-01

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Field	Value	Language
dc.contributor.author	Tran, TN
dc.contributor.author	Selinger, CI
dc.contributor.author	Kohonen-Corish, MRJ
dc.contributor.author	McCaughan, B
dc.contributor.author	Kennedy, C
dc.contributor.author	O'Toole, SA
dc.contributor.author	Cooper, WA
dc.date.accessioned	2022-08-20T07:52:46Z
dc.date.available	2015-08-11
dc.date.available	2022-08-20T07:52:46Z
dc.date.issued	2016-01
dc.identifier.citation	Clin Lung Cancer, 2016, 17, (1), pp. 30-8.e1
dc.identifier.issn	1525-7304
dc.identifier.issn	1938-0690
dc.identifier.uri	http://hdl.handle.net/10453/160563
dc.description.abstract	INTRODUCTION: Mesenchymal epithelial transition factor (MET) is a promising therapeutic target in non-small-cell lung cancer (NSCLC) but there are limited data about MET alterations in treatment-naive NSCLC and whether or not these changes are consistent between primary tumors and metastases. We aimed to investigate concordance, clinicopathological correlations, and prognostic value of MET alterations in primary NSCLC and corresponding nodal metastases. MATERIALS AND METHODS: MET gene copy number (GCN) status was evaluated using fluorescent in situ hybridization (FISH) and MET protein expression using immunohistochemistry (IHC) in tissue microarray sections from a retrospective cohort of 300 surgically resected NSCLCs including 93 cases with nodal metastases. RESULTS: Primary NSCLCs were MET IHC positive in 28 (10.3%) of cases and MET FISH positive (high polysomy or amplification) in 22 (8.1%) but only 1 (0.4%) showed amplification. In metastases, high MET GCN (18.3%) and protein expression (21.3%) was more frequent compared with primary tumors. The status of MET in lymph nodes significantly correlated with MET status in the corresponding primary tumors. Squamous cell carcinomas showed lower MET overexpression compared with nonsquamous tumors but there were no other associations with clinicopathological characteristics. Patients with tumors that were either MET FISH positive or IHC positive had a significantly better overall survival in univariate and multivariate analyses. CONCLUSION: Alterations of MET are more commonly seen in nodal metastases than primary tumors and this might have implications for their utility as predictive biomarkers to select patients for MET inhibition. MET overexpression and MET high polysomy occur in a low proportion of primary NSCLCs and is associated with a good prognosis.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	CIG MEDIA GROUP, LP
dc.relation.ispartof	Clin Lung Cancer
dc.relation.isbasedon	10.1016/j.cllc.2015.08.002
dc.rights	info:eu-repo/semantics/closedAccess
dc.subject	1103 Clinical Sciences, 1112 Oncology and Carcinogenesis
dc.subject.classification	Oncology & Carcinogenesis
dc.subject.mesh	Adenocarcinoma
dc.subject.mesh	Adult
dc.subject.mesh	Aged
dc.subject.mesh	Aged, 80 and over
dc.subject.mesh	Biomarkers, Tumor
dc.subject.mesh	Carcinoma, Large Cell
dc.subject.mesh	Carcinoma, Non-Small-Cell Lung
dc.subject.mesh	Carcinoma, Squamous Cell
dc.subject.mesh	Case-Control Studies
dc.subject.mesh	Female
dc.subject.mesh	Follow-Up Studies
dc.subject.mesh	Gene Dosage
dc.subject.mesh	Humans
dc.subject.mesh	Immunoenzyme Techniques
dc.subject.mesh	In Situ Hybridization, Fluorescence
dc.subject.mesh	Lung Neoplasms
dc.subject.mesh	Lymphatic Metastasis
dc.subject.mesh	Male
dc.subject.mesh	Middle Aged
dc.subject.mesh	Neoplasm Grading
dc.subject.mesh	Neoplasm Invasiveness
dc.subject.mesh	Neoplasm Staging
dc.subject.mesh	Prognosis
dc.subject.mesh	Proto-Oncogene Proteins c-met
dc.subject.mesh	Retrospective Studies
dc.subject.mesh	Survival Rate
dc.subject.mesh	Tissue Array Analysis
dc.subject.mesh	Humans
dc.subject.mesh	Adenocarcinoma
dc.subject.mesh	Carcinoma, Large Cell
dc.subject.mesh	Carcinoma, Non-Small-Cell Lung
dc.subject.mesh	Carcinoma, Squamous Cell
dc.subject.mesh	Lung Neoplasms
dc.subject.mesh	Neoplasm Invasiveness
dc.subject.mesh	Lymphatic Metastasis
dc.subject.mesh	Neoplasm Staging
dc.subject.mesh	Immunoenzyme Techniques
dc.subject.mesh	Prognosis
dc.subject.mesh	Tissue Array Analysis
dc.subject.mesh	In Situ Hybridization, Fluorescence
dc.subject.mesh	Survival Rate
dc.subject.mesh	Case-Control Studies
dc.subject.mesh	Retrospective Studies
dc.subject.mesh	Follow-Up Studies
dc.subject.mesh	Gene Dosage
dc.subject.mesh	Adult
dc.subject.mesh	Aged
dc.subject.mesh	Aged, 80 and over
dc.subject.mesh	Middle Aged
dc.subject.mesh	Female
dc.subject.mesh	Male
dc.subject.mesh	Proto-Oncogene Proteins c-met
dc.subject.mesh	Neoplasm Grading
dc.subject.mesh	Biomarkers, Tumor
dc.title	Alterations of MET Gene Copy Number and Protein Expression in Primary Non-Small-Cell Lung Cancer and Corresponding Nodal Metastases.
dc.type	Journal Article
utslib.citation.volume	17
utslib.location.activity	United States
utslib.for	1103 Clinical Sciences
utslib.for	1112 Oncology and Carcinogenesis
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
utslib.copyright.status	closed_access	*
dc.date.updated	2022-08-20T07:52:44Z
pubs.issue	1
pubs.publication-status	Published
pubs.volume	17
utslib.citation.issue	1

Abstract:

INTRODUCTION: Mesenchymal epithelial transition factor (MET) is a promising therapeutic target in non-small-cell lung cancer (NSCLC) but there are limited data about MET alterations in treatment-naive NSCLC and whether or not these changes are consistent between primary tumors and metastases. We aimed to investigate concordance, clinicopathological correlations, and prognostic value of MET alterations in primary NSCLC and corresponding nodal metastases. MATERIALS AND METHODS: MET gene copy number (GCN) status was evaluated using fluorescent in situ hybridization (FISH) and MET protein expression using immunohistochemistry (IHC) in tissue microarray sections from a retrospective cohort of 300 surgically resected NSCLCs including 93 cases with nodal metastases. RESULTS: Primary NSCLCs were MET IHC positive in 28 (10.3%) of cases and MET FISH positive (high polysomy or amplification) in 22 (8.1%) but only 1 (0.4%) showed amplification. In metastases, high MET GCN (18.3%) and protein expression (21.3%) was more frequent compared with primary tumors. The status of MET in lymph nodes significantly correlated with MET status in the corresponding primary tumors. Squamous cell carcinomas showed lower MET overexpression compared with nonsquamous tumors but there were no other associations with clinicopathological characteristics. Patients with tumors that were either MET FISH positive or IHC positive had a significantly better overall survival in univariate and multivariate analyses. CONCLUSION: Alterations of MET are more commonly seen in nodal metastases than primary tumors and this might have implications for their utility as predictive biomarkers to select patients for MET inhibition. MET overexpression and MET high polysomy occur in a low proportion of primary NSCLCs and is associated with a good prognosis.

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