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Gene amplification and overexpression of HER2 in renal cell carcinoma
Z Latif1, A D Watters, J M S Bartlett
1Department of Surgery, Glasgow Royal Infirmary, Glasgow, UK. zaklatif@hotmail.com
Objective:
To determine the frequency of HER2 genetic abnormalities in renal cell carcinoma (RCC) and hence assess the potential suitability of Herceptin immunotherapy.
Patients And Methods:
Tumours from 27 patients with RCC were assessed; all patients had undergone nephrectomy. Benign renal tissue from the nephrectomy specimens was studied in seven patients. Gene amplification was assessed using fluorescent in-situ hybridization, and protein over-expression using immunohistochemistry.
Results:
Twenty-four patients had clear cell renal carcinoma, two had papillary renal carcinoma and one a sarcomatoid variant carcinoma. There was no HER2 amplification in the tumours or the benign renal tissue. Polysomy 17 was detected in 11 of 27 tumours (41%) and increased HER2 copy number in seven (26%). Both polysomy 17 and increased HER2 copy number were absent in the benign renal tissue. Three tumours (11%) and six of the seven benign renal tissue samples over-expressed the HER2 protein.
Conclusions:
HER2 amplification is absent and protein over-expression uncommon in RCC. This casts doubt on the suitability of Herceptin in the treatment of RCC.
Insights
HER2 amplification is absent in renal cell carcinoma (RCC), though some tumors show polysomy 17 or increased HER2 copy number. HER2 protein over-expression is uncommon, questioning Herceptin
Area of Science:
- Oncology
- Genetics
- Immunotherapy
Background:
- Renal cell carcinoma (RCC) is a significant cancer.
- HER2 (Human Epidermal growth factor Receptor 2) is a target in some cancers.
- Herceptin is an immunotherapy targeting HER2.
Purpose of the Study:
- To investigate the frequency of HER2 genetic abnormalities in RCC.
- To evaluate the potential of Herceptin for RCC treatment based on HER2 status.
Main Methods:
- Analysis of 27 RCC tumor samples and 7 benign renal tissues.
- Fluorescent in-situ hybridization (FISH) for gene amplification.
- Immunohistochemistry (IHC) for protein over-expression.
Main Results:
- No HER2 gene amplification detected in RCC or benign tissues.
- Polysomy 17 (41%) and increased HER2 copy number (26%) found in RCC tumors.
- HER2 protein over-expression was uncommon in tumors (11%) but present in benign tissue (6/7).
Conclusions:
- HER2 amplification is absent in renal cell carcinoma.
- HER2 protein over-expression is uncommon in RCC, limiting Herceptin's potential efficacy.
- Further research may be needed to explore alternative therapeutic targets.