期刊
JOURNAL OF TRANSLATIONAL MEDICINE
卷 13, 期 -, 页码 -出版社
BMC
DOI: 10.1186/s12967-015-0633-7
关键词
Head and neck squamous cell carcinoma (HNSCC); EGFR; MET; HGF; Cetuximab; Prognostic factor
资金
- Spanish Ministerio de Economia y Competitividad (MINECO) (AES Program) [PI12/01552]
- Ministerio de Sanidad (Cancer Network)
- Comunidad de Madrid [S2010/BMD-2344]
- MINECO (Instituto de Salud Carlos III, RETICS Red de Biobancos)
- FEDER funds [RD09/0076/00101]
- same Biobanks initiative
Background: Activation of the MET oncogene promotes tumor growth, invasion and metastasis in several tumor types. Additionally, MET is activated as a compensatory pathway in the presence of EGFR blockade, thus resulting in a mechanism of resistance to EGFR inhibitors. Methods: We have investigated the impact of HGF and MET expression, MET activation (phosphorylation), MET gene status, and MET-activating mutations on cetuximab sensitivity in recurrent or metastatic squamous cell carcinoma of the head and neck (HNSCC) patients. Results: A single-institution retrospective analysis was performed in 57 patients. MET overexpression was detected in 58 % patients, MET amplification in 39 % and MET activation (p-MET) in 30 %. Amplification was associated with MET overexpression. Log-rank testing showed significantly worse outcomes in recurrent/metastatic, MET overexpressing patients for progression-free survival and overall survival. Activation of MET was correlated with worse PFS and OS. In multivariate logistic regression analysis, p-MET was an independent prognostic factor for PFS. HGF overexpression was observed in 58 % patients and was associated with MET phosphorylation, suggesting a paracrine activation of the receptor. Conclusions: HGF/MET pathway activation correlated with worse outcome in recurrent/metastatic HNSCC patients. When treated with a cetuximab-based regimen, these patients correlated with worse outcome. This supports a dual blocking strategy of HGF/MET and EGFR pathways for the treatment of patients with recurrent/metastatic HNSCC.
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