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Patient-derived Orthotopic Xenograft Models for Human Urothelial Cell Carcinoma and Colorectal Cancer Tumor Growth and Spontaneous Metastasis
Published on: May 12, 2019
HER2 overexpression in muscle-invasive urothelial carcinoma of the bladder: prognostic implications
Stefan Krüger1, Georg Weitsch, Hartwig Büttner
1Institute of Pathology, Medical University of Lübeck, Lübeck, Germany. krueger@patho.mu-luebeck.de
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.
Insights
HER2 receptor overexpression is common in muscle-invasive bladder cancer, impacting survival. This finding supports exploring trastuzumab therapy for bladder tumors expressing HER2.
Area of Science:
- Oncology
- Urothelial Carcinomas
- Molecular Diagnostics
Background:
- The HER2 (c-erbB-2) receptor is overexpressed in various human cancers.
- Trastuzumab, a monoclonal antibody targeting HER2, is effective in HER2-positive breast carcinoma.
- Muscle-invasive urothelial cell carcinoma of the urinary bladder represents a significant clinical challenge.
Purpose of the Study:
- To evaluate the immunohistochemical expression of HER2 in a large cohort of muscle-invasive bladder carcinomas.
- To correlate HER2 expression with clinicopathological features and patient survival.
- To determine if HER2 status is an independent prognostic factor in this patient group.
Main Methods:
- Retrospective analysis of 138 patients undergoing radical cystectomy for muscle-invasive bladder carcinoma.
- Immunohistochemical assessment of HER2 expression using the FDA-approved HercepTest.
- Statistical analysis including Kaplan-Meier curves and multivariate analysis.
Main Results:
- HER2 overexpression was detected in 41% (57/138) of tumors, more frequent in high-grade carcinomas.
- No significant association found between HER2 overexpression and tumor stage or lymph node status.
- Patients with HER2-overexpressing tumors exhibited significantly worse disease-related survival (p=0.034).
- HER2 status (p=0.020) and lymph node status (p=0.0001) were independent predictors of survival.
Conclusions:
- HER2 overexpression is a frequent finding in muscle-invasive bladder cancer.
- HER2 status provides additional prognostic information beyond traditional factors.
- Clinical trials investigating trastuzumab efficacy in HER2-positive bladder carcinoma are warranted.
