Die Her2/neu-Expression beim lokal fortgeschrittenen Harnblasenkarzinom: Ansatz für eine molekulare Therapie?
| Autor: | Martin Bögemann, Elke Eltze, C. Wülfing, S. Bierer, D. von Struensee, Lothar Hertle |
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| Rok vydání: | 2005 |
| Předmět: |
Pathology
medicine.medical_specialty Bladder cancer business.industry Angiogenesis Urology medicine.medical_treatment medicine.disease_cause medicine.disease HercepTest Metastasis Targeted therapy Cystectomy Cancer research Medicine Immunohistochemistry skin and connective tissue diseases business Carcinogenesis |
| Zdroj: | Aktuelle Urologie. 36:423-429 |
| ISSN: | 1438-8820 0001-7868 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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