Ach, Tobias and Zeitler, Katharina and Schwarz-Furlan, Stephan and Baader, Katharina and Agaimy, Abbas and Rohrmeier, Christian and Zenk, Johannes and Gosau, Martin and Reichert, Torsten E. and Brockhoff, Gero and Ettl, Tobias (2013) Aberrations of MET are associated with copy number gain of EGFR and loss of PTEN and predict poor outcome in patients with salivary gland cancer. VIRCHOWS ARCHIV, 462 (1). pp. 65-72. ISSN 0945-6317,
Full text not available from this repository. (Request a copy)Abstract
Hepatocyte growth factor receptor (MET) is a key driver of oncogenic transformation. Copy number gain and amplification of MET positively enhance tumour growth, invasiveness and metastasis in different cancer types. In the present study, 266 carcinomas of the major and minor salivary glands were investigated for genomic MET status by fluorescence in situ hybridization and for protein expression by immunohistochemistry. Results were matched with clinicopathological parameters, long-term survival and the status of epidermal growth factor receptor (EGFR) and phosphatase and tensin homologue (PTEN). Low polysomy (n=42), high polysomy (n=27), amplification (n=2) and deletion (n=18) were found as aberrations of genomic MET in certain subtypes. MET aberrations were associated with increased patient age (>70 years, p=0.003), male gender (p=0.01), increased tumour size (p=0.002), lymph node metastases (p<0.001), high-grade malignancy (p<0.001) and unfavourable overall survival (p<0.001). Both copy number gain (p<0.001) and deletion (p=0.031) of MET correlated with copy number gain of EGFR. Tumours with genomic loss of PTEN (n=48) concurrently presented aberration of genomic MET (p<0.001). MET gene status significantly correlated with protein status (p=0.038). In conclusion, gain but also loss of genomic MET activity correlates with aggressive tumour growth, nodal metastasis and worse overall survival in salivary gland cancer. Moreover, aberrations of MET are associated with EGFR and PTEN signalling and might possess relevance for targeted therapies of salivary gland carcinomas in the future.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CELL LUNG-CANCER; HEPATOCYTE GROWTH-FACTOR; IN-SITU HYBRIDIZATION; ADENOID CYSTIC CARCINOMA; C-MET; ACQUIRED-RESISTANCE; PROGNOSTIC-FACTORS; KINASE INHIBITORS; SIGNALING PATHWAY; BREAST-CANCER; Salivary gland cancer; MET; EGFR; PTEN; Prognosis |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Frauenheilkunde und Geburtshilfe (Schwerpunkt Geburtshilfe) Medicine > Lehrstuhl für Hals-Nasen-Ohren-Heilkunde Medicine > Lehrstuhl für Mund-, Kiefer- und Gesichtschirurgie Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 29 Apr 2020 08:22 |
| Last Modified: | 29 Apr 2020 08:22 |
| URI: | https://pred.uni-regensburg.de/id/eprint/17485 |
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