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MET overexpression, amplification linked to worse prognosis for gastroesophageal adenocarcinoma
MET amplification and overexpression — measured by immunohistochemistry, spectrometry-based selected reaction monitoring and fluorescence in situ hybridization — were associated with a worse prognosis for gastroesophageal adenocarcinoma, according to study findings.
“The findings are consistent with some smaller studies demonstrating similar concordance patterns between Met protein overexpression (MET/Met) spectrometry–based selected reaction monitoring (SRM) and immunohistochemistry and/or fluorescence in situ hybridization (FISH) and comparable adverse prognoses in univariate analyses when the Met biomarker was positive,” Daniel V.T. Catenacci, MD, medical oncologist in the section of hematology/oncology, department of medicine at University of Chicago, and colleagues wrote.
The researchers evaluated 447 formalin-fixed, paraffin-embedded gastroesophageal adenocarcinoma samples obtained from University of Chicago or University of Urbino in Italy between 2000 to 2015. The relationship between MET gene amplification and MET/Met status and OS were measured via FISH, immunohistochemistry and SRM, to characterize any prognostic value of MET/Met for gastroesophageal adenocarcinoma.
MET FISH — regardless of the definition of amplification — was a poor prognostic marker via univariate analyses. Patients who were amplification positive had shorter median OS compared with unamplified patients. This included amplification-positive patients with a MET/CEP7 ratio of at least 2 (17.8 months vs. 68.7 months; HR = 3.13; 95% CI, 1.84-5.33), patients with a mean MET gene copy number of at least 5 (28.7 months vs. 68.7 months; HR = 2.51; 95% CI, 1.45-4.34), and patients for whom at least 10% of tumor cells had 15 or more copies of MET (17.8 months vs. 59.4 months; HR = 4.28; 95% CI, 2.18-8.39).
Similar observations were made with Met protein overexpression via immunohistochemistry, defined by 1+ or greater intensity inmore than25% of the tumor cell membrane (54.2 months vs. 78.4 months; HR = 1.39; 95% CI, 1.04-1.86) and via SRM results of 400 amol/g or greater (22.6 months vs. 59.4 months; HR = 1.76; 95% CI, 0.06-2.9).
In addition, a greater proportion of samples with FISH amplification had an esophageal primary location (16.3%) compared with a distal gastric location (3.7%).
A significant correlation was observed between MET FISH/Met immunohistochemistry, MET FISH/Met SRM, and Met immunohistochemistry/Met SRM. However, only MET FISH and Met SRM were independent negative prognostic biomarkers in multivariate analyses.
“The results of this study suggest that amplification by FISH and/or overexpression by SRM should be incorporated into multivariate models when one is assessing the prognostic significance of other novel covariates,” the researchers concluded. “Moreover, amplification and overexpression, as determined by FISH and SRM, may better direct treatment and, in particular, Met–targeted therapies for gastroesophageal adenocarcinoma principally in the setting of next-generation clinical trial designs.” – by Melinda Stevens
Disclosure : Catenacci reports honoraria for advisory boards/consultant roles from Amgen, Genentech/Roche, Lilly Oncology and OncoPlexDx/NantOmics; and research funding from Amgen, Genentech and OncoPlexDx/NantOmics. Please see the full study for a list of other researchers’ relevant financial disclosures.