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. 2011 May;20(5):1021-7.
doi: 10.1158/1055-9965.EPI-10-1080. Epub 2011 Mar 10.

MET expression and amplification in patients with localized gastric cancer

Yelena Y Janjigian  1 , Laura H Tang, Daniel G Coit, David P Kelsen, Todd D Francone, Martin R Weiser, Suresh C Jhanwar, Manish A Shah
Affiliations

MET expression and amplification in patients with localized gastric cancer

Yelena Y Janjigian et al. Cancer Epidemiol Biomarkers Prev. 2011 May.

Abstract

Background: MET, the receptor for hepatocyte growth factor, has been proposed as a therapeutic target in gastric cancer. This study assessed the incidence of MET expression and gene amplification in tumors of Western patients with gastric cancer.

Methods: Tumor specimens from patients enrolled on a preoperative chemotherapy study (NCI 5700) were examined for the presence of MET gene amplification by FISH, MET mRNA expression by quantitative PCR, MET overexpression by immunohistochemistry (IHC), and for evidence of MET pathway activation by phospho-MET (p-MET) IHC.

Results: Although high levels of MET protein and mRNA were commonly encountered (in 63% and 50% of resected tumor specimens, respectively), none of these tumors had MET gene amplification by FISH, and only 6.6% had evidence of MET tyrosine kinase activity by p-MET IHC.

Conclusions: In this cohort of patients with localized gastric cancer, the presence of high MET protein and RNA expression does not correlate with MET gene amplification or pathway activation, as evidenced by the absence of amplification by FISH and negative p-MET IHC analysis.

Impact: This article shows a lack of MET amplification and pathway activation in a cohort of 38 patients with localized gastric cancer, suggesting that MET-driven gastric cancers are relatively rare in Western patients.

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Figures

Figure 1
Figure 1. Representative interphase FISH analysis of a gastric tumor sample without MET amplification
The MET signal in red is associated with eight individual copies of chromosome 7 centromere in green (polyploidy).
Figure 2
Figure 2. MET protein expression in gastric carcinoma by immunohistochemistry
Positive MET immunoreactivity was identified in a moderately differentiated intestinal-type adenocarcinoma with cytoplasmic staining pattern (A). In contrast, MET reactivity was not observed in a poorly differentiated mucinous adenocarcinoma with signet ring cell features (original magnification ×200).
Figure 3
Figure 3. phospho-MET (p-MET) protein expression in gastric carcinoma by immunohistochemistry
Positive p-MET immunoreactivity was demonstrated in a portion of a moderately to poorly differentiated adenocarcinoma (A) (lower left) and was negative in other areas of the same tumor (upper right). The staining pattern was membranous as well as cytoplasmic although the immunoreactivity was not seen in all the cells (B) (original magnification was X100 for A and X200 for B).
See this image and copyright information in PMC

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