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HER-2 and TOP2A coamplification in urinary bladder cancer
Ronald Simon1, Ramin Atefy, Urs Wagner
1Institute for Pathology and Urologic Clinics, University of Basel, Basel, Switzerland. ronald_simon_de@yahoo.de
International Journal of Cancer
|October 21, 2003
Summary
HER-2/NEU and TOP2A gene amplifications are common in advanced bladder cancer. HER-2 amplification often involves TOP2A alterations, impacting tumor stage, grade, and survival.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- HER-2/NEU is a frequently amplified oncogene and therapeutic target in bladder cancer.
- TOP2A, a gene targeted by anticancer drugs, is often coamplified with HER-2 in breast cancer.
Purpose of the Study:
- To investigate the amplification and expression of TOP2A and HER-2 in bladder cancer.
- To analyze associations between these genes, tumor phenotype, and clinical outcomes.
Main Methods:
- Analysis of 2,317 bladder tumor samples using a tissue microarray.
- Fluorescence in situ hybridization (FISH) and immunohistochemistry were employed.
Main Results:
- HER-2 amplification occurred in 6.3% and TOP2A in 1.5% of tumors, predominantly in advanced stages.
- 56% of HER-2 amplified tumors showed TOP2A alterations, including coamplification (14.7%).
- Both amplifications correlated with advanced stage, high grade, and protein overexpression. TOP2A alterations were linked to poorer survival in muscle-invasive tumors.
Conclusions:
- HER-2 amplifications in bladder cancer are frequently associated with TOP2A gene alterations.
- The 17q12-q21 amplicon's structure may influence responses to HER-2 or TOP2A targeted therapies.