In conclusion, these results strongly suggest that tpr-met activation does not play a role in Caucasian gastric carcinogenesis, while overexpression of the c-met gene occurs in the majority of Caucasian gastric adenocarcinomas.
MET amplification was associated with adenocarcinomas (P = 0.007), high-grade tumors (P = 0.003), more sites of metastasis, higher BRAF mutation, and PTEN loss (all P < 0.05).
The lung cancer subtypes share some genetic variations such as the dysfunction of tumor suppressor gene TP53, and also harbor specific variations of their own such as MET in ADC, FGFR1 and FGFR3 in SCC and MYC in SCLC.
Sanchez-Vega and colleagues prospectively demonstrate that both intra- and intertumoral differential expression of the receptor tyrosine kinases HER2, EGFR, and MET dictate sensitivity to the pan-HER inhibitor afatinib in a phase II trial of trastuzumab-refractory <i>HER2</i>-amplified gastroesophageal adenocarcinomas.
In the subgroup of adenocarcinoma and squamous cell carcinoma patients with stage IIA-IIIB disease, the prognostic impact of c-MET was significant in the univariate analysis (HR = 0.60, 95% CI: 0.43-0.83).
There was a clear relationship between c-met protein staining and higher grade adenocarcinomas (p < 0.001). c-met protein is frequently detected in PIN and higher grade prostate cancers; future studies should evaluate the biological significance of these findings.
MET exon 14 alterations, which result in increased MET protein levels due to disrupted ubiquitin-mediated degradation, occur at a prevalence of around 3% in adenocarcinomas and around 2% in other lung neoplasms, making them attractive targets for the treatment of lung cancer.
Multivariate analysis showed SDC (p = .002) to be the strongest predictor of lymph node metastasis, followed by MET aberration (p = .009), T3/T4 classification (p = .017), PTEN deletion (p = .042), and adenocarcinoma not otherwise specified (NOS; p = .047).
CUP adenocarcinomas and poorly differentiated carcinomas harboured the highest frequency of variants in genes involved in signal transduction pathways (e.g.MET, EGFR, HRAS, KRAS, and BRAF).
The MET gene had increased copy numbers in 9.88% of the NSCL adenocarcinoma patients; 3.49% of MET mutations in NSCL adenocarcinoma included 3 intron mutations.
In conclusion, MET abnormalities can be found in a small group of patients with GE adenocarcinoma and further studies are necessary to better characterize the prognostic and predictive impact of MET alterations.