HER2/neu overexpression in the development of muscle-invasive transitional cell carcinoma of the bladder

Latif, Z., Watters, A.D., Dunn, I., Grigor, K.M., Underwood, M.A. and Bartlett, J.M.S. (2003) HER2/neu overexpression in the development of muscle-invasive transitional cell carcinoma of the bladder. British Journal of Cancer, 89(7), pp. 1305-1309. (doi: 10.1038/sj.bjc.6601245)

Abstract

The mortality from transitional cell carcinoma (TCC) of the urinary bladder increases significantly with the progression of superficial or locally invasive disease (pTa/pT1) to detrusor muscle-invasive disease (pT2+). The most common prognostic markers in clinical use are tumour stage and grade, which are subject to considerable intra- and interobserver variation. Polysomy 17 and HER2/neu gene amplification and protein overexpression have been associated with more advanced disease. Standardised techniques of fluorescence in situ hybridisation and immunohistochemistry, which are currently applied to other cancers with a view to offering anti-HER2/neu therapies, were applied to tumour pairs comprising pre- and postinvasive disease from 25 patients undergoing treatment for bladder cancer. In the preinvasive tumours, increased HER2/neu copy number was observed in 76% of cases and increased chromosome 17 copy number in 88% of cases, and in the postinvasive group these values were 92 and 96%, respectively (not significantly different P=0.09 and 0.07, respectively). HER2 gene amplification rates were 8% in both groups. Protein overexpression rates were 76 and 52%, respectively, in the pre- and postinvasive groups (P=0.06). These results suggest that HER2/neu abnormalities occur prior to and persist with the onset of muscle-invasive disease. Gene amplification is uncommon and other molecular mechanisms must account for the high rates of protein overexpression. Anti-HER2/neu therapy might be of use in the treatment of TCC.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Underwood, Mr Mark
• Authors: Latif, Z., Watters, A.D., Dunn, I., Grigor, K.M., Underwood, M.A., and Bartlett, J.M.S.
• Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer); R Medicine > RB Pathology
• College/School: College of Medical Veterinary and Life Sciences
• Journal Name: British Journal of Cancer
• ISSN: 0007-0920