title: A new system for substaging pT1 papillary bladder cancer: a prognostic evaluation.
abstract: Superficially invasive (pT1) papillary urothelial cell carcinomas (UCCs) may run a variable course. Several attempts have been made for the substaging of UCC to identify the clinically aggressive tumors. We present a new substaging system, based on the extent of invasion. From a series of 53 primary pT1 UCC, 24 cases showed invasion of the subepithelial stroma by an invasive front extending more than a maximum length of 0.5 mm (pT1mic), and 29 showed extensively (>0.5 mm) infiltrating UCC (pT1ext). We tested diagnostic reproducibility between 2 pathologists and found 81% agreement. Furthermore, all cases were analyzed for mutations in the fibroblast growth factor receptor 3 (FGFR3) gene, which represents the favorable pathway of urothelial cell carcinogenesis. Mutant FGFR3 was commonly observed in pT1mic UCC (15/24, 63%), but rarely (2/29, 7%) in pT1ext UCC (chi2 test, P < .001). The presence of pT1ext at initial diagnosis proved to be the strongest predictor for progression, also when adjusted for FGFR3 mutation status in a Cox regression model. If confirmed on a larger series of pT1 UCC, this relatively simple and new substaging system for pT1 UCC may prove to be of prognostic value and supportive to clinical decision-making.
authors.affiliation: Department of Pathology, Erasmus MC, Rotterdam 300 DR, The Netherlands.
authors.forename: Madelon N M
authors.initials: MN
authors.lastname: van der Aa
authors.forename: Geert J L H
authors.initials: GJ
authors.lastname: van Leenders
authors.forename: Ewout W
authors.initials: EW
authors.lastname: Steyerberg
authors.forename: Bas W
authors.initials: BW
authors.lastname: van Rhijn
authors.forename: Adriaan C
authors.initials: AC
authors.lastname: Jöbsis
authors.forename: Ellen C
authors.initials: EC
authors.lastname: Zwarthoff
authors.forename: Theodorus H
authors.initials: TH
authors.lastname: van der Kwast
mesh_terms: D000368:Aged; D002291:Carcinoma, Papillary / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging / Q000379:methods*; D011379:Prognosis; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D051498:Receptor, Fibroblast Growth Factor, Type 3; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000473:pathology*
chemical_list: D017468:Receptors, Fibroblast Growth Factor; C496365:FGFR3 protein, human; D011505:Protein-Tyrosine Kinases; D051498:Receptor, Fibroblast Growth Factor, Type 3