title: HER2 overexpression in muscle-invasive urothelial carcinoma of the bladder: prognostic implications.
abstract: The HER2 (c-erbB-2) receptor is overexpressed in a variety of human malignant tumors and, in breast carcinoma, has been identified as a target for anti-HER2-directed therapy with the monoclonal antibody (MAb) trastuzumab. The aim of this retrospective study was to evaluate immunohistochemic HER2 expression in a large cohort of muscle-invasive urothelial cell carcinomas of the urinary bladder and to compare the results to pathologic characteristics and survival. Paraffin-embedded tumor specimens from 138 patients undergoing radical cystectomy for muscle-invasive bladder carcinoma were studied immunohistochemically with the Food and Drug Administration (FDA)-approved HercepTest (Dako, Glostrup, Denmark). HER2 overexpression was observed in 57 of 138 tumors (41%) and occurred more frequently in high-grade carcinomas than in low-grade carcinomas (p = 0.036). No significant relationship with HER2 overexpression was registered for tumor staging and lymph node status. Kaplan-Meier curves showed a significantly worse disease-related survival (p = 0.034) in patients with HER2-overexpressing tumors compared to those without HER2 overexpression. In addition to lymph node status (p = 0.0001; relative risk [RR] = 2.93), HER2 status (p = 0.020; RR = 2.22) was identified as an independent predictor for disease-related survival in a multivariate analysis. These results suggest that HER2 expression might provide additional prognostic information in patients with muscle-invasive bladder carcinomas. Because many of these patients harbor HER2-overexpressing tumors, clinical trials evaluating the efficacy of trastuzumab in bladder carcinoma are warranted.
authors.affiliation: Institute of Pathology, Medical University of Lübeck, Lübeck, 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; D014408:Biomarkers, Tumor; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009132:Muscles; D009361:Neoplasm Invasiveness; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D012189:Retrospective Studies; D012306:Risk; D016019:Survival Analysis; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000473:pathology; D019459:Urothelium
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases