[Current knowledge in molecular pathology of urothelial cancer].
Results of molecular pathology have supported changes in the 2004 WHO classification of urothelial cancer. Since then new molecular data such as the distribution pattern of the fibroblast growth factor receptor 3 (FGFR3) has further supported the principle of low and high grade entities of urothelial carcinoma. Animal experiments with knockout mice and conditional knockout systems reveal important parallels to humans and results emphasize the cellular context as a trigger for malignancy. One special feature of the urothelium is its high protection of the urothelial cells by members of the retinoblastoma gene family, efficiently inhibiting invasion even in the presence of p53 mutations. In search of the tumor stem cell phenotype the basal cell phenotype is the focus of attention providing a high clonogenic potential. At the same time detailed analysis of the distribution of mutations in the mitochondrial genome within the urothelium will help to gain insight into the spreading of normal cell or tumor cell clones. The overall data in urological oncology provide evidence that diagnostic and prognostic tools for urothelial cancer can only be reached with multiparametric approaches.
Knüchel-Clarke
R
R
Institut für Pathologie, Medizinische Fakultät der RWTH Aachen, Pauwelsstr. 30, 52074 Aachen. rknuechel-clarke@ukaachen.de
Dahl
E
E
Gaisa
N T
NT
Schwamborn
K
K
Lindemann-Docter
K
K
Henkel
C
C
D000818:Animals; D002295:Carcinoma, Transitional Cell / Q000235:genetics* / Q000473:pathology*; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004252:DNA Mutational Analysis; D016161:Genes, Retinoblastoma / Q000235:genetics; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D009363:Neoplasm Proteins / Q000235:genetics; D009367:Neoplasm Staging; D014411:Neoplastic Stem Cells / Q000473:pathology; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology*; D019459:Urothelium / Q000473:pathology
C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins; D016159:Tumor Suppressor Protein p53; C496365:FGFR3 protein, human; D051498:Receptor, Fibroblast Growth Factor, Type 3