Virchows Archiv

, Volume 462, Issue 1, pp 65–72

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

  • Tobias Ach
  • Katharina Zeitler
  • Stephan Schwarz-Furlan
  • Katharina Baader
  • Abbas Agaimy
  • Christian Rohrmeier
  • Johannes Zenk
  • Martin Gosau
  • Torsten E. Reichert
  • Gero Brockhoff
  • Tobias Ettl
Original Article

DOI: 10.1007/s00428-012-1358-0

Cite this article as:
Ach, T., Zeitler, K., Schwarz-Furlan, S. et al. Virchows Arch (2013) 462: 65. doi:10.1007/s00428-012-1358-0

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.

Keywords

Salivary gland cancerMETEGFRPTENPrognosis

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Tobias Ach
    • 1
  • Katharina Zeitler
    • 2
  • Stephan Schwarz-Furlan
    • 3
  • Katharina Baader
    • 1
  • Abbas Agaimy
    • 3
  • Christian Rohrmeier
    • 4
  • Johannes Zenk
    • 5
  • Martin Gosau
    • 1
  • Torsten E. Reichert
    • 1
  • Gero Brockhoff
    • 6
  • Tobias Ettl
    • 1
  1. 1.Department of Oral and Maxillofacial SurgeryUniversity of RegensburgRegensburgGermany
  2. 2.Department of PathologyUniversity of RegensburgRegensburgGermany
  3. 3.Department of PathologyUniversity of Erlangen-NurembergErlangenGermany
  4. 4.Department of OtorhinolaryngologyUniversity of RegensburgRegensburgGermany
  5. 5.Department of OtorhinolaryngologyUniversity of Erlangen-NurembergErlangenGermany
  6. 6.Department of Gynecology and ObstetricsUniversity of RegensburgRegensburgGermany