PMID- 12647367 OWN - NLM STAT- MEDLINE DCOM- 20030417 LR - 20171116 IS - 0070-4113 (Print) IS - 0070-4113 (Linking) VI - 86 DP - 2002 TI - [HER-2 and TOP 2A gene amplifications in urinary bladder carcinoma]. PG - 176-83 AB - The HER-2/neu gene is frequently amplified in bladder cancer. Topoisomerase 2 Alpha (TOP2A) which is located nearby the HER-2/neu gene is an important molecular target for several anti cancer drugs. The frequency of TOP2A amplification in urinary bladder cancer is unknown. It was the aim of this study to determine the frequency of HER-2 and TOP2A amplification in urinary bladder cancer and to evaluate the association of these amplifications with tumor phenotype. For this purpose a tissue microarray containing 768 pTa, 425 pT1 and 571 pT2-4 carcinomas was analyzed by fluorescence in situ hybridization (FISH). Amplifications of both genes were significantly associated with advanced tumor stage and high grade. HER-2 amplification was found in 1.6% of pTa, 7.2% of pT1 and 13.8% of pT2-4 carcinomas (p < 0.0001). HER-2 amplification was present in only 1.1% of grade 1 and 0.8% of grade 2 tumors but in 14.2% of grade 3 tumors (p < 0.0001). TOP2A amplification was present in 0.7% pTa, 1.8% pT1 and 3.4% pT2-4 carcinomas (p < 0.0001). TOP2A was found in none of the grade 1, in 0.2% of grade 2 and 3.8% of grade 3 tumors (p < 0.0001). 1% of all analyzed tumors had simultaneously high level amplification of TOP2A and HER-2. Amplification of both genes were significantly associated with tumor specific survival if all tumors were analyzed together. Given the high frequency of HER-2 amplification in urinary bladder cancer, some of these tumors may respond favorable to Herceptin therapy. The TOP2A amplification status may influence response to anthracyclin treatment. FAU - Simon, R AU - Simon R AD - Institut fur Pathologie und Urologische Klinik, Universitat Basel, Schweiz. FAU - Atefy, R AU - Atefy R FAU - Wagner, U AU - Wagner U FAU - Forster, T AU - Forster T FAU - Fijan, A AU - Fijan A FAU - Bruderer, J AU - Bruderer J FAU - Wilber, K AU - Wilber K FAU - Mihatsch, M J AU - Mihatsch MJ FAU - Gasser, T AU - Gasser T FAU - Sauter, G AU - Sauter G LA - ger PT - Journal Article PT - Review TT - HER-2 und TOP 2A Genamplifikationen beim Harnblasenkarzinom. PL - Germany TA - Verh Dtsch Ges Pathol JT - Verhandlungen der Deutschen Gesellschaft fur Pathologie JID - 7503704 RN - 0 (Antigens, Neoplasm) RN - 0 (DNA-Binding Proteins) RN - 0 (Poly-ADP-Ribose Binding Proteins) RN - EC 5.99.1.3 (DNA Topoisomerases, Type II) RN - EC 5.99.1.3 (TOP2A protein, human) SB - IM MH - Antigens, Neoplasm MH - DNA Topoisomerases, Type II/*genetics MH - DNA-Binding Proteins MH - Gene Amplification MH - Genes, erbB-2/*genetics MH - Humans MH - Poly-ADP-Ribose Binding Proteins MH - Urinary Bladder Neoplasms/enzymology/*genetics RF - 36 EDAT- 2003/03/22 04:00 MHDA- 2003/04/18 05:00 CRDT- 2003/03/22 04:00 PHST- 2003/03/22 04:00 [pubmed] PHST- 2003/04/18 05:00 [medline] PHST- 2003/03/22 04:00 [entrez] PST - ppublish SO - Verh Dtsch Ges Pathol. 2002;86:176-83.