title: Numerical aberrations of chromosome 17 and the 9p21 locus are independent predictors of tumor recurrence in non-invasive transitional cell carcinoma of the urinary bladder.
abstract: Since the majority of patients with non-invasive (stage pTa) bladder carcinoma experience tumor recurrence, the identification of prognostic markers for assessing the biologic behavior of tumors is of high clinical interest. In this retrospective study, we investigated the prognostic value of numerical aberrations of chromosomes 3, 7, 17 and of the 9p21 gene locus in 71 pTa bladder carcinomas using the UroVysion test. This recently developed multi-probe fluorescence in situ hybridization (FISH) test, which simultaneously stains the 9p21 locus and the centromer regions of chromosomes 3, 7 and 17, was applied on paraffin sections from formalin-fixed tumor specimens. All tumors were evaluated for twelve different criteria, among which were: polysomy 3, 7 or 17 in > or =10% of tumor cells, pentasomy or higher polysomy 3, 7 or 17 in > or =1 tumor cell, and loss of both 9p21 alleles in > or =10% of tumor cells. The latter parameter was the most frequent chromosomal aberration (detected in 83% of the tumors), while polysomies 3, 7 and 17 were registered in 27, 13 and 12% of the cases, respectively. Most of the parameters were found at higher frequencies in G3 tumors compared to G1 or G2 tumors. None of the parameters correlated with progression-free survival, but polysomy 3 (p=0.029), polysomy of at least one of the chromosomes 3, 7 or 17 (p=0.032), pentasomy/higher polysomy 17 (p=0.007), and loss of 9p21 (p=0.026), correlated significantly with recurrence-free survival. Of these, pentasomy/higher polysomy 17 (p=0.015) and loss of 9p21 (p=0.036) were identified as independent predictors of tumor recurrence in a multivariate Cox regression analysis that also included tumor grade. In conclusion, we suggest that evaluation of numerical aberrations of chromosome 17 and the 9p21 locus may represent a useful tool to assess tumor recurrence of pTa bladder carcinomas more accurately.
authors.affiliation: Institute of Pathology, University of Lübeck, Ratzeburger Allee 160, D-23538 Lübeck, Germany. krueger@patho.mu-luebeck.de
authors.forename: Stefan
authors.initials: S
authors.lastname: Krüger
authors.forename: Franziska
authors.initials: F
authors.lastname: Mess
authors.forename: Andreas
authors.initials: A
authors.lastname: Böhle
authors.forename: Alfred C
authors.initials: AC
authors.lastname: Feller
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002295:Carcinoma, Transitional Cell / Q000235:genetics*; D002869:Chromosome Aberrations; D002886:Chromosomes, Human, Pair 17 / Q000648:ultrastructure*; D002899:Chromosomes, Human, Pair 9 / Q000648:ultrastructure*; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D012008:Recurrence; D013997:Time Factors; D001749:Urinary Bladder Neoplasms / Q000235:genetics*