c-MET Overexpression as a Poor Predictor of MET Amplifications or Exon 14 Mutations in Lung Sarcomatoid Carcinomas

Abstract

IHC is not a relevant screening tool for MET abnormalities in LSC.

The EMT transcription factor, Twist1, as a novel therapeutic target for pulmonary sarcomatoid carcinomas

“…These tumours have a strong association with tobacco exposure. The clinical behaviour of PSCs is extremely aggressive, and patient prognosis is extremely poor (2,3), since these tumours have a high rate of distant metastasis. The effect of conventional chemotherapy for PSCs remains controversial due to their low incidence (4); thus, progress on tumour treatments is moderate.…”

MET IHC Is a Poor Screen for MET Amplification or MET Exon 14 Mutations in Lung Adenocarcinomas: Data from a Tri-Institutional Cohort of the Lung Cancer Mutation Consortium

“…Recently, MET IHC was shown to correlate poorly with MET/CEP7 ratio in all stages of sarcomatoid lung cancer studied. 8 In this tri-institutional cohort of patients with metastatic lung adenocarcinoma, more than one of three cases were MET IHC-positive, but only 2% were MET-amplified. MET IHC also did not detect MET in two of the three MET-amplified cases.…”

“…6,7 Moreover, there is growing evidence that MET IHC may not be a good screening test for MET amplification or METex14 mutation in lung cancer. 8 The Lung Cancer Mutation Consortium 2 (LCMC2) was a multi-institutional effort established in 2010 to investigate the frequency of oncogenic drivers in lung adenocarcinoma. 9 Using a tri-institutional cohort derived from the LCMC experience (University of Colorado, Dana Farber Cancer Institute, and Memorial Sloan Kettering Cancer Center), we set out to determine the association of MET IHC testing with MET amplification or METex14 mutation status in patients with metastatic lung adenocarcinomas.…”

MET Amplification (MET/CEP7 Ratio ≥ 1.8) Is an Independent Poor Prognostic Marker in Patients With Treatment-naive Non–Small-cell Lung Cancer

“…Some investigators have used MET gene copy number (GCN), [19][20][21] others have used the MET/CEP7 ratio, [22][23][24] whereas most investigators have used both the GCN and the MET/CEP7 ratio. 11,[25][26][27][28][29][30][31][32][33][34] The cut-off values of MET GCN or the MET/CEP7 ratio used to define MET amplification also have been variable among studies, including MET copy number ≥5 19,20 ; MET/CEP7 ratio ≥1.8 25,28 , ≥2 25,26 or ≥ 2.2 22,23 ; or ratio ≥2 plus MET copy number ≥5. 27,31,33 Some investigators have further classified MET amplification into three tiers or levels: low (ratio, 1.8 to 2.2), intermediate (ratio, >2.2 to<5), and high (ratio, ≥5).…”

“…11,[25][26][27][28][29][30][31][32][33][34] The cut-off values of MET GCN or the MET/CEP7 ratio used to define MET amplification also have been variable among studies, including MET copy number ≥5 19,20 ; MET/CEP7 ratio ≥1.8 25,28 , ≥2 25,26 or ≥ 2.2 22,23 ; or ratio ≥2 plus MET copy number ≥5. 27,31,33 Some investigators have further classified MET amplification into three tiers or levels: low (ratio, 1.8 to 2.2), intermediate (ratio, >2.2 to<5), and high (ratio, ≥5). 28,35 These highly variable criteria used to define MET amplification in the literature complicate comparisons of the frequency of MET amplification, response to the therapy, and patient outcomes, and the association of MET amplification with patients' survival remains controversial.…”