PMID- 12370744 OWN - NLM STAT- MEDLINE DCOM- 20030304 LR - 20141120 IS - 1019-6439 (Print) IS - 1019-6439 (Linking) VI - 21 IP - 5 DP - 2002 Nov TI - Overexpression of c-erbB-2 oncoprotein in muscle-invasive bladder carcinoma: relationship with gene amplification, clinicopathological parameters and prognostic outcome. PG - 981-7 AB - Amplification of the c-erbB-2 oncogene and protein overexpression are well-known in breast cancer and a basis for therapy with the monoclonal antibody trastuzumab, which binds to the receptor encoded by c-erbB-2. Regarding bladder carcinoma, several studies have examined c-erbB-2 expression, but their results are quite heterogeneous. In the present study, we evaluated the expression of this oncoprotein immunohistochemically in 203 muscle-invasive urothelial bladder carcinomas using the HercepTest. Additionally, 42 cases were studied for gene amplification by fluorescence in situ hybridization (FISH) using the PathVysion kit. Follow-up was known in 147 patients. The results were compared with pathologic characteristics and disease-related survival. Immunohistochemical c-erbB-2 overexpression was observed in 37% of the tumors (76/203). However, only 5% (2/42) showed amplification of the oncogene, indicating that predominantly other mechanisms than gene amplification may cause protein overexpression in bladder cancer. C-erbB-2 protein overexpression was significantly associated with high tumor grade (p=0.004) and infiltrative growth pattern (p=0.0001), and tendentiously associated with the presence of lymph node metastases (p=0.077). Regarding tumor stage, sex and age, no significant correlation was registered. Kaplan-Meier curves showed a significantly worse disease-related survival for patients with c-erbB-2 overexpressing tumors (p=0.0346 by log-rank test). Multivariate analysis revealed that, besides nodal status (p=0.0001) and tumor stage (p=0.028), c-erbB-2 overexpression was an independent predictor of disease-related survival (p=0.030). Thus, our results suggest that immunohistochemical c-erbB-2 detection might represent an additional tool in determining bladder cancer prognosis. Clinical trials evaluating the efficacy of trastuzumab therapy in bladder cancer patients are warranted. FAU - Kruger, Stefan AU - Kruger S AD - Institut fur Pathologie, Universitatsklinikum Lubeck, Ratzeburger Allee 160, D-23538 Lubeck, Germany. krueger@patho.mu-luebeck.de FAU - Weitsch, Georg AU - Weitsch G FAU - Buttner, Hartwig AU - Buttner H FAU - Matthiensen, Arne AU - Matthiensen A FAU - Bohmer, Torsten AU - Bohmer T FAU - Marquardt, Tim AU - Marquardt T FAU - Sayk, Friedhelm AU - Sayk F FAU - Feller, Alfred C AU - Feller AC FAU - Bohle, Andreas AU - Bohle A LA - eng PT - Journal Article PL - Greece TA - Int J Oncol JT - International journal of oncology JID - 9306042 RN - EC 2.7.10.1 (Receptor, ErbB-2) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Female MH - *Gene Amplification MH - Humans MH - Immunohistochemistry MH - In Situ Hybridization, Fluorescence MH - Male MH - Middle Aged MH - Muscles MH - Neoplasm Invasiveness MH - Prognosis MH - Receptor, ErbB-2/*analysis MH - Urinary Bladder Neoplasms/*chemistry/genetics/pathology EDAT- 2002/10/09 04:00 MHDA- 2003/03/05 04:00 CRDT- 2002/10/09 04:00 PHST- 2002/10/09 04:00 [pubmed] PHST- 2003/03/05 04:00 [medline] PHST- 2002/10/09 04:00 [entrez] PST - ppublish SO - Int J Oncol. 2002 Nov;21(5):981-7.