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

• Published in: British journal of cancer Vol. 89; no. 7; pp. 1305 - 1309
• Main Authors: Latif, Z, Watters, A D, Dunn, I, Grigor, K M, Underwood, M A, Bartlett, J M S
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 06.10.2003; Nature Publishing Group
• Subjects: Adult; Aged; Aged, 80 and over; Biological and medical sciences; Biomarkers, Tumor - analysis; Biomedical and Life Sciences; Biomedicine; Bladder cancer; Cancer Research; Carcinoma, Transitional Cell - metabolism; Carcinoma, Transitional Cell - pathology; Chromosomes; Chromosomes, Human, Pair 17 - genetics; Disease Progression; Drug Resistance; Epidemiology; Female; Gene Amplification; Gene Dosage; Humans; Immunoenzyme Techniques; In Situ Hybridization, Fluorescence; Kinases; Male; Medical prognosis; Medical research; Medical sciences; Middle Aged; Molecular and Cellular Pathology; Molecular Medicine; Mortality; Neoplasm Invasiveness; Nephrology. Urinary tract diseases; Oncology; Proteins; Receptor, ErbB-2 - genetics; Receptor, ErbB-2 - metabolism; Surgery; Tumors; Tumors of the urinary system; Urinary Bladder Neoplasms - metabolism; Urinary Bladder Neoplasms - pathology; Urinary tract. Prostate gland; United Kingdom > UK; oncogenes; transitional cell carcinoma; Human; Urinary system disease; Gene overexpression; Tumorous infiltration; Malignant tumor; Urinary tract disease; Transitional cell carcinoma; HER2/neu; Gene amplification; Urinary bladder; C-Onc gene; Detrusor muscle; Genetics; Bladder disease; Protooncogene
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6601245

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.