HER-2 and TOP2A coamplification in urinary bladder cancer
| Autor: | Ronald Simon, Urs Wagner, Thomas Forster, Guido Sauter, Michael J. Mihatsch, André Fijan, Ramin Atefy, James Bruderer, Thomas Gasser, Kim Wilber |
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| Rok vydání: | 2003 |
| Předmět: |
Cancer Research
Receptor ErbB-2 Biology Breast cancer Antigens Neoplasm Gene duplication medicine Humans Poly-ADP-Ribose Binding Proteins In Situ Hybridization Fluorescence Neoplasm Staging Tissue microarray Urinary bladder Bladder cancer Gene Amplification Amplicon Genes erbB-2 medicine.disease Prognosis Chromosome 17 (human) DNA-Binding Proteins Gene Expression Regulation Neoplastic medicine.anatomical_structure DNA Topoisomerases Type II Oncology Urinary Bladder Neoplasms Cancer research Immunohistochemistry Cell Division |
| Zdroj: | International journal of cancer. 107(5) |
| ISSN: | 0020-7136 |
| Popis: | HER-2/NEU is one of the most frequently amplified oncogenes and a potential therapeutic target in bladder cancer. In breast cancer, the adjacent TOP2A gene, the molecular target for several anticancer drugs, is frequently coamplified together with HER-2. To study the amplification and expression of TOP2A and HER-2 and associations with tumor phenotype and clinical outcome in bladder cancer, a tissue microarray containing 2,317 bladder tumor samples was analyzed by FISH and immunohistochemistry. Overall amplification frequencies were 6.3% for HER-2 and 1.5% for TOP2A. Amplifications were most frequently seen in advanced-stage (pT2-4) tumors (HER-2 13.8%, TOP2A 3.4%). Of HER-2-amplified tumors, 56% also had alterations of TOP2A, including 14.7% coamplifications, 33.3% gains and 8% deletions. Only 17.6% of TOP2A amplifications occurred independently of HER-2 alterations. Both HER-2 and TOP2A amplifications were significantly associated with advanced tumor stage (HER-2 p < 0.0001, TOP2A p = 0.0218), high grade (p < 0.0001 for both) and protein overexpression (p < 0.0001 for both). TOP2A amplification and overexpression were linked to shortened survival in muscle-invasive tumors (p = 0.0042 and 0.0077, respectively). In summary, our data suggest that HER-2 amplifications are frequently linked to alterations of the TOP2A gene in bladder cancer. The anatomy of the 17q12-q21 amplicon may be important for response to therapies targeting HER-2 or TOP2A. |
| Databáze: | OpenAIRE |
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