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Genomic aberrations of MDM 2, MDM 4, FGFR 1 and FGFR 3 are associated with poor outcome in patients with salivary gland cancer
Author(s) -
Ach Tobias,
SchwarzFurlan Stephan,
Ach Stephanie,
Agaimy Abbas,
Gerken Michael,
Rohrmeier Christian,
Zenk Johannes,
Iro Heinrich,
Brockhoff Gero,
Ettl Tobias
Publication year - 2016
Publication title -
journal of oral pathology and medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.887
H-Index - 83
eISSN - 1600-0714
pISSN - 0904-2512
DOI - 10.1111/jop.12394
Subject(s) - polysomy , biology , fluorescence in situ hybridization , cancer research , aneuploidy , malignancy , metastasis , trisomy , microbiology and biotechnology , cancer , chromosome , genetics , gene
Fibroblast growth factor receptor 1 and 3 ( FGFR 1, FGFR 3) impact on tissue homoeostasis, embryonic development and carcinogenesis. Murine double minute protein 4 ( MDM 4) and mouse double minute 2 homologue ( MDM 2) are regulators of p53‐protein and may be the origin of an apoptosis overpowering cascade. A collective of 266 carcinomas of salivary glands were investigated for MDM 2, MDM 4, FGFR 1 and FGFR 3 aberrations by fluorescence in situ hybridization ( FISH ). The results were matched with clinicopathological parameters and with expression of PTEN and p53. MDM 2 gene amplification ( n = 9) and chromosomal aberrations (trisomy, n = 47; high polysomy, n = 7) are linked to high‐grade malignancy ( P < 0.001), lymph node metastasis ( P = 0.001), advanced tumour size ( P = 0.013) and stage ( P < 0.001), gender ( P = 0.002) and age ( P = 0.001). MDM 4 gene amplification ( n = 19) and chromosomal aberrations (trisomy, n = 34; high polysomy, n = 31) are correlated to high‐grade malignancy ( P < 0.001), lymph node metastasis ( P = 0.008), advanced tumour size ( P = 0.039), stage ( P = 0.004) and loss of PTEN ( P < 0.001). Only, high‐grade malignancy ( P < 0.001), lymph node metastasis ( P = 0.036) and advanced tumour stage ( P = 0.025) are associated with FGFR 3 amplification ( n = 1) or chromosomal aberrations (low polysomy, n = 61; high polysomy, n = 55) but not with MDM 4 alterations. FGFR 1 amplifications ( n = 5) and chromosomal aberrations (trisomy, n = 38; high polysomy, n = 30) are associated with high‐grade malignancy ( P < 0.001), advanced tumour size ( P = 0.026) and stage ( P = 0.004), gender ( P = 0.016) and age ( P = 0.023). Aberrations of MDM 2, MDM 4, FGFR 1 and FGFR 3 correlate with aggressive tumour growth and nodal metastasis. MDM 2 ( P < 0.001), MDM 4 ( P = 0.005) and FGFR 3 ( P = 0.006) alterations are associated with worse overall survival of patients with salivary gland cancer.