title: Immunohistochemical and molecular characterizations in urothelial carcinoma of bladder in patients less than 45 years.
abstract: Bladder tumours in early-onset patients are rare and seem to exhibit unique clinicopathological features. Only few studies have investigated somatic alterations in this specific age of onset group and evidence is accumulating of a distinct molecular behaviour of early-onset bladder tumours. We collected the largest cohort of early-onset tumours of patients 45 years old or younger and aimed to test genomic alterations typically found in bladder cancer. Tumours of 118 early-onset patients were compared with a consecutive group of 113 cases. Immunohistochemistry of TP53, CK20 and Ki-67 was carried out. Molecular analysis was conducted to test for loss of heterozygosity of chromosome 9 and 17, as well asTP53andFGFR3mutations. Fisher´s exact and chi-squared test were appropriately used. No differences in grade/stage characteristics were observed. Overexpressed TP53 was differentially distributed between the two groups. TP53 nuclear accumulation was significantly more frequent in early-onset papillomas, PUNLMPs and pTa low-grade tumours compared to the consecutive cohort (p=0.005). Moreover, chromosome 9 deletions (29.5% vs. 44.6%) andFGFR3mutations (34.5% vs. 63.7%) were less often detected in early-onset patients (p=0.05 andp<0.0001). By comparing the largest cohort of early-onset bladder cancer patients with an unselected group, we demonstrated that the typical molecular features are not independent of age at diagnosis. Our study supports the hypothesis of a distinct biological behaviour in early-onset tumours.
authors.affiliation: Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Veronika
authors.initials: V
authors.lastname: Weyerer
authors.affiliation: Department of Internal Medicine II, University Medical Center Regensburg, Regensburg, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Schneckenpointner
authors.affiliation: Department of Urology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Filbeck
authors.affiliation: St Josef Medical Center, Department of Urology, University of Regensburg, Regensburg, Germany.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Burger
authors.affiliation: Tumor Center Regensburg, University of Regensburg, Regensburg, Germany.
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Hofstaedter
authors.affiliation: Department of Pathology and Molecular Pathology, University Hospital Zurich, Zurich 8091, Switzerland.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Wild
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Samson W
authors.initials: SW
authors.lastname: Fine
authors.affiliation: Department of Pathology, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Humphrey
authors.affiliation: Division of Anatomic and Molecular Pathology, Department of Pathology and Immunology, St. Louis Children's Hospital, Washington University Medical Center, St. Louis, MO, USA.
authors.forename: Louis P
authors.initials: LP
authors.lastname: Dehner
authors.affiliation: Department of Pathology & Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Mahul B
authors.initials: MB
authors.lastname: Amin
authors.affiliation: Pathology Nordhessen, Kassel, Germany.
authors.forename: Josef
authors.initials: J
authors.lastname: Rüschoff
authors.affiliation: Institute of Pathology, SRH-Klinikum, Gera, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Boltze
authors.affiliation: Institute for Pathology, Ruhr-University, Bochum, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Tannapfel
authors.affiliation: Department of Pathology, Erasmus Medical Centre, Rotterdam, the Netherlands.
authors.forename: Ellen
authors.initials: E
authors.lastname: Zwarthoff
authors.affiliation: Department of Surgery, Cordoba University Medical School, Cordoba, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Lopez-Beltran
authors.affiliation: Section of Pathological Anatomy, Polytechnic University of the Marche Region, School of Medicine, United Hospitals, Ancona, Italy.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Montironi
authors.affiliation: Institute of Pathology, Medical University of Graz, Graz, Austria.
authors.forename: Cord
authors.initials: C
authors.lastname: Langner
authors.affiliation: Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Stoehr
authors.affiliation: Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Arndt
authors.initials: A
authors.lastname: Hartmann
authors.affiliation: Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Giedl
keywords: Bladder cancer; Early-onset; FGFR3; Mutation analysis.; TP53 positivity