Gene amplification and overexpression of HER2 in renal cell carcinoma

Abstract

Objective To determine the frequency of HER2 genetic abnormalities in renal cell carcinoma (RCC) and hence assess the potential suitability of Herceptin TM 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 ampli®cation was assessed using¯uorescent 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 ampli®cation 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 ampli®cation is absent and protein over-expression uncommon in RCC. This casts doubt on the suitability of Herceptin TM in the treatment of RCC.

Close association between HER-2 amplification and overexpression in human tumors of non-breast origin

“…For example HER-2 positivity has been observed in 0-100% of renal and prostate cancers. 22,23 Such controversial data makes it evident that, for most cancer types, true HER-2 alteration frequencies can hardly be obtained from the literature. Therefore, we analyzed more than 3000 tumors of 120 different tumor subtypes under fully standardized conditions.…”

Biologic and therapeutic role of HER2 in cancer

“…The highest frequency of HER2 overexpression is found in inflammatory breast cancers scoring 3 þ with herceptest in more than 60% of the cases (Tagliabue et al, 1998), followed by Wilm's tumor (50%), bladder cancer (44%), and noninflammatory breast cancer (25%). In other tumors, including pancreatic, colon, ovary, and lung tumors, the frequency of HER2 overexpression differs in different reports and is often greater than predicted by gene-amplification data (Kim et al, 2000;Geddert et al, 2002;Goebel et al, 2002;Hirsch et al, 2002;Khan et al, 2002;Latif et al, 2002;Soule et al, 2002;Yan et al, 2002;Nakamura et al, 2003), suggesting that overexpression in these tumors is due to gene deregulation rather than gene amplification. New therapeutic tools targeting HER2 are now being investigated mainly for therapy of breast carcinomas, in which overexpression is mainly due to gene amplification.…”

Genome-wide DNA copy number predictors of lapatinib sensitivity in tumor-derived cell lines

“…Although substantial activity has not been seen in unselected patients in phase II studies of lung and colorectal cancers (36), a retrospective analysis of a phase III study in renal cell cancer suggests benefit in patients whose tumors markedly overexpress EGFR (amplification of HER2 is extremely rare in renal cell cancer; ref. 37). …”