title: Overexpression of c-erbB-2 oncoprotein in muscle-invasive bladder carcinoma: relationship with gene amplification, clinicopathological parameters and prognostic outcome.
abstract: 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.
authors.affiliation: Institut fur Pathologie, Universitatsklinikum Lubeck, Ratzeburger Allee 160, D-23538 Lubeck, Germany. krueger@patho.mu-luebeck.de
authors.forename: Stefan
authors.initials: S
authors.lastname: Krüger
authors.forename: Georg
authors.initials: G
authors.lastname: Weitsch
authors.forename: Hartwig
authors.initials: H
authors.lastname: Büttner
authors.forename: Arne
authors.initials: A
authors.lastname: Matthiensen
authors.forename: Torsten
authors.initials: T
authors.lastname: Böhmer
authors.forename: Tim
authors.initials: T
authors.lastname: Marquardt
authors.forename: Friedhelm
authors.initials: F
authors.lastname: Sayk
authors.forename: Alfred C
authors.initials: AC
authors.lastname: Feller
authors.forename: Andreas
authors.initials: A
authors.lastname: Böhle
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005784:Gene Amplification; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009132:Muscles; D009361:Neoplasm Invasiveness; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D001749:Urinary Bladder Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000473:pathology
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases