title: HER2/neu overexpression in the development of muscle-invasive transitional cell carcinoma of the bladder.
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.
authors.affiliation: University Department of Surgery, Level II, Queen Elizabeth Building, Glasgow Royal Infirmary, Glasgow G31 2ER, UK.
authors.forename: Z
authors.initials: Z
authors.lastname: Latif
authors.forename: A D
authors.initials: AD
authors.lastname: Watters
authors.forename: I
authors.initials: I
authors.lastname: Dunn
authors.forename: K M
authors.initials: KM
authors.lastname: Grigor
authors.forename: M A
authors.initials: MA
authors.lastname: Underwood
authors.forename: J M S
authors.initials: JM
authors.lastname: Bartlett
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D002295:Carcinoma, Transitional Cell / Q000378:metabolism* / Q000473:pathology; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D018450:Disease Progression; D005260:Female; D005784:Gene Amplification; D018628:Gene Dosage; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases