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Updated: Aug 15, 2026
An Orthotopic Bladder Cancer Model for Gene Delivery Studies
Published on: December 1, 2013
[Expression of Her2/neu in locally advanced bladder cancer: implication for a molecular targeted therapy]
C Wülfing1, D von Struensee, S Bierer
1Klinik und Poliklinik für Urologie, Universitätsklinik Münster. wulfing@uni-muenster.de
Purpose:
The Her2/neu oncoprotein, belonging to the erbB-receptor family, is known to contribute to physiological mechanisms of cell proliferation by intrinsic tyrosine-kinase-activity. Overexpression has been shown for several tumors and is known to influence malignant cell proliferation, metastasis and angiogenesis. The clinical use of Her2-targeting agents has emerged in clinical research. In our study, we analyzed Her2/neu expression in urothelial tumors.
Materials And Methods:
Her2/neu expression was evaluated immunohistochemically (IHC) in 127 patients undergoing radical cystectomy (DAKO- Herceptest). Additionally, fluorescent-in-situ-hybridisation (FISH) was carried out in all immunohistochemically "2+" cases (n = 41) to assess gene amplification. After grading the Her2/neu-overall status, Her2/neu expression was correlated with clinicopathological parameters and survival data.
Results:
An immunohistochemical Her2/neu expression was found in 95 of 127 cases (74.8 %). Of all 41 cases with "2+" staining (32.2 %), 11 cases (26.8 %) showed positive amplification by FISH. Therefore, including the IHC 3+ cases, a Her2/neu overall status of 22 positive (17.3 %) tumors was assessed. Correlation with clinical data showed a relation to lymph node metastasis (P = 0.06), lymph vessel invasion (P = 0.07) and metastasis (P = 0.002). No further associations with other parameters nor with overall survival (P = 0.73) or disease-free survival (P = 0.63) were found.
Conclusions:
Her2/neu upregulation is found in invasive bladder cancer with significant differences in protein expression and gene amplification. The association with lymphogenic and distant metastases implicates a late event in carcinogenesis. Moreover, there was no further association with clinicopathological parameters and survival. The possible role of a molecular targeted therapy of advanced bladder cancer with Her2/neu targeting agents should be assessed in further clinical trials.
Insights
Her2/neu protein overexpression and gene amplification occur in invasive bladder cancer, correlating with metastasis. Further trials are needed to assess Her2-targeting therapies for advanced disease.
Area of Science:
- Oncology
- Molecular Biology
- Urothelial Carcinomas
Background:
- The Her2/neu oncoprotein (erbB-receptor family) drives cell proliferation via tyrosine kinase activity.
- Overexpression is linked to malignant proliferation, metastasis, and angiogenesis in various tumors.
- Her2-targeting agents are emerging in clinical research for cancer treatment.
Purpose of the Study:
- To analyze Her2/neu expression in urothelial tumors.
- To correlate Her2/neu expression with clinicopathological parameters and survival data.
Main Methods:
- Immunohistochemistry (IHC) evaluated Her2/neu expression in 127 radical cystectomy patients.
- Fluorescent in situ hybridization (FISH) assessed gene amplification in IHC "2+" cases (n=41).
- Her2/neu status was correlated with clinical data and survival outcomes.
Main Results:
- Her2/neu expression detected in 74.8% of tumors by IHC.
- Gene amplification found in 26.8% of IHC "2+" cases via FISH.
- A Her2/neu overall positive status was found in 17.3% of tumors, associated with lymph node metastasis (P=0.06), lymph vessel invasion (P=0.07), and distant metastasis (P=0.002).
Conclusions:
- Her2/neu upregulation is present in invasive bladder cancer, with distinct protein expression and gene amplification.
- Association with metastases suggests a late role in carcinogenesis.
- No significant correlation with other clinicopathological parameters or survival was observed, warranting further clinical trials for Her2-targeting therapies.
