posters International Association for Breast Cancer Research 2014

Incidence of c-MET gene amplification and protein expression in triple negative breast cancer patients, and correlation to clinicopathological features  (#12)

Rhiannon Beckers 1 2 3 , Christina Selinger 1 , Jane Beith 1 4 , Wendy Cooper 1 5 6 , Thang Tran 1 , Alexander Swarbrick 7 , Sandra O'Toole 1 5 7
  1. Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia
  2. Department of Pathology, University of Sydney, Camperdown, NSW, Australia
  3. Department of Science, University of Technology Sydney, Ultimo, NSW, Australia
  4. Department of Oncology, Chris O'Brien Lifehouse, Royal Prince Alfred Hospital, Camperdown, NSW, Australia
  5. Sydney Medical School, University of Sydney, Camperdown, NSW, Australia
  6. School of Medicine, University of Western Sydney, Campbelltown, NSW, Australia
  7. Garvan Institute of Medical Research, The Kinghorn Cancer Centre, Darlinghurst, NSW, Australia

Aims: There is emerging data from large scale breast cancer genomic studies that overexpression and/or amplification of the tyrosine kinase receptor c-MET may occur in Triple negative breast cancer (TNBC) but there has been limited validation in an independent cohort. We determined the incidence of c-MET gene amplification and over-expression and clinicopathological associations in a cohort of 89 TNBC patients.
Methods: A cohort of 89 triple negative breast cancers and 10 normal mammary tissue samples were analysed for MET copy number by fluorescence in situ hybridisation. Cases with a MET/CEP7 ratio >2 or a copy number ≥4 were classed as positive for MET amplification. MET protein expression was analysed in 89 triple negative breast cancer cases. Tissue cores were scored for percentage of cells expressing protein, and intensity of the stain: 0 (negative), 1+ (weak), 2+ (moderate) or 3+ (strong) by a specialist pathologist.
Results: FISH scores could be obtained in 79 of the TNBC cases. Only one case (1.3%) showed elevated copy number for MET but also showed increased CEP7 signals (average MET = 9.2, average CEP7 = 7.8, ratio = 1.2) and was therefore deemed co-amplified. MET immunohistochemistry could be assessed in 87 patients, with 52.9% showing c-MET protein expression. Only a single case showed strong (3+) c-MET protein expression (1.2%), with 42.5% showing weak (+1) expression, and 9.2% showing moderate (+2) expression. Fisher’s exact test was performed and no significant correlations were found.
Discussion: Interestingly, the case showing high protein expression was found to have a MET/CEP7 ratio of only 1.1, and the co-amplified case was scored as 1+ for protein expression. Amplification of MET was a rare event in our cohort occurring in a single patient only, however aberrant expression of MET protein was more common, seen in 52.9% of the cohort and may be worthy of further investigation.