Immunohistochemical and molecular characterizations in urothelial carcinoma of bladder in patients less than 45 years

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 as TP53 and FGFR3 mutations. 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%) and FGFR3 mutations (34.5% vs. 63.7%) were less often detected in early-onset patients (p=0.05 and p<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.

Journal of Cancer. 2017 Feb 05*** epublish ***

Veronika Weyerer, Roland Schneckenpointner, Thomas Filbeck, Maximilian Burger, Ferdinand Hofstaedter, Peter J Wild, Samson W Fine, Peter A Humphrey, Louis P Dehner, Mahul B Amin, Josef Rüschoff, Carsten Boltze, Andrea Tannapfel, Ellen Zwarthoff, Antonio Lopez-Beltran, Rodolfo Montironi, Cord Langner, Robert Stoehr, Arndt Hartmann, Johannes Giedl

Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany., Department of Internal Medicine II, University Medical Center Regensburg, Regensburg, Germany., Department of Urology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany., St Josef Medical Center, Department of Urology, University of Regensburg, Regensburg, Germany., Tumor Center Regensburg, University of Regensburg, Regensburg, Germany., Department of Pathology and Molecular Pathology, University Hospital Zurich, Zurich 8091, Switzerland., Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Department of Pathology, Yale University School of Medicine, New Haven, CT, USA., Division of Anatomic and Molecular Pathology, Department of Pathology and Immunology, St. Louis Children's Hospital, Washington University Medical Center, St. Louis, MO, USA., Department of Pathology & Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA., Pathology Nordhessen, Kassel, Germany., Institute of Pathology, SRH-Klinikum, Gera, Germany., Institute for Pathology, Ruhr-University, Bochum, Germany., Department of Pathology, Erasmus Medical Centre, Rotterdam, the Netherlands., Department of Surgery, Cordoba University Medical School, Cordoba, Spain., Section of Pathological Anatomy, Polytechnic University of the Marche Region, School of Medicine, United Hospitals, Ancona, Italy., Institute of Pathology, Medical University of Graz, Graz, Austria.