Format

Send to

Choose Destination
Diagn Pathol. 2015 Jul 28;10:130. doi: 10.1186/s13000-015-0362-5.

Improved diagnostics targeting c-MET in non-small cell lung cancer: expression, amplification and activation?

Author information

1
Clinical and Experimental Pathology, Research Center Borstel, Borstel, Germany. i.watermann@lungenclinic.de.
2
LungenClinic Grosshansdorf, Grosshansdorf, Germany. i.watermann@lungenclinic.de.
3
Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), Borstel, Germany. i.watermann@lungenclinic.de.
4
Clinical and Experimental Pathology, Research Center Borstel, Borstel, Germany.
5
Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), Borstel, Germany.
6
Pathology, Faculty of Medicine, Alexandria University, Alexandria, Egypt.
7
LungenClinic Grosshansdorf, Grosshansdorf, Germany.
8
Ludwig Maximilians University (LMU), Munich, Germany.
9
Comprehensive Pneumology Center Munich, (CPC-M), Member of the German Center for Lung Research, Thoracic Oncology Centre Munich, Munich, Germany.
10
Institute of Pathology, Heidelberg University, Heidelberg, Germany.
11
Translational Lung Research Center (TLRC), Member of the German Center for Lung Research, Heidelberg, Germany.
12
Medical Clinic, Research Center Borstel, Borstel, Germany.
13
Institute of Pathology, Hannover Medical School, Hanover, Germany.
14
Biomedical Research in Endstage and Obstructive Lung Disease Hanover (BREATH), Member of the German Center for Lung Research, Munich, Germany.

Abstract

BACKGROUND:

Several c-MET targeting inhibitory molecules have already shown promising results in the treatment of patients with Non-small Cell Lung Cancer (NSCLC). Combination of EGFR- and c-MET-specific molecules may overcome EGFR tyrosine kinase inhibitor (TKI) resistance. The aim of this study was to allow for the identification of patients who might benefit from TKI treatments targeting MET and to narrow in on the diagnostic assessment of MET.

METHODS:

222 tumor tissues of patients with NSCLC were analyzed concerning c-MET expression and activation in terms of phosphorylation (Y1234/1235 and Y1349) using a microarray format employing immunohistochemistry (IHC). Furthermore, protein expression and MET activation was correlated with the amplification status by Fluorescence in Situ Hybridization (FISH).

RESULTS:

Correlation was observed between phosphorylation of c-MET at Y1234/1235 and Y1349 (spearman correlation coefficient rs = 0.41; p < 0.0001). No significant correlation was shown between MET expression and phosphorylation (p > 0.05). c-MET gene amplification was detected in eight of 214 patients (3.7%). No significant association was observed between c-MET amplification, c-MET protein expression and phosphorylation.

CONCLUSION:

Our data indicate, that neither expression of c-MET nor the gene amplification status might be the best way to select patients for MET targeting therapies, since no correlation with the activation status of MET was observed. We propose to take into account analyzing the phosphorylation status of MET by IHC to select patients for MET targeting therapies. Signaling of the receptor and the activation of downstream molecules might be more crucial for the benefit of therapeutics targeting MET receptor tyrosine kinases than expression levels alone.

PMID:
26215852
PMCID:
PMC4517562
DOI:
10.1186/s13000-015-0362-5
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for BioMed Central Icon for PubMed Central
Loading ...
Support Center