THE RAT BLADDER-TUMOR MODEL SYSTEM RBT RESEMBLES PHENOTYPICALLY AND CYTOGENETICALLY HUMAN SUPERFICIAL TRANSITIONAL-CELL CARCINOMA

A cohort of 300 ACI rats was kept under standard laboratory conditions. After 30 months or upon natural death, complete autopsy was performed. In the genitourinary tract four kidney and five bladder tumors were found. Two of these bladder tumors, RBT323 and RBT157, are serially transplantable. In the fifth transplant generation the RBT323 tumor becomes metastatic to the lungs in more than 90% of animals. The metastatic ability of the RBT157 tumor changes from low to intermediate (50% of the rats have lung metastases) in the fourth passage. Histologically, the initial passages of the RBT323 and 157 tumors are grade II transitional cell carcinoma (TCC). The histological pattern of the RBT157 tumor remains essentially unchanged, whereas the RBT323 tumor progresses to a grade III tumor in the third passage. Electron microscopical studies reveal oblong elliptical and round vesicles lined by an asymmetrical unit membrane in the tumor cells, which stresses the urothelial origin. of the tumors. Immunohistochemically both tumors show expression of cytokeratin 5, 7, 8 and 18. The progression of the tumors to a metastatic phenotype, however, is not associated with a specific change in the morphological characteristics. Cytogenetic analysis shows that both tumors are peridiploid with few. marker chromosomes. Interestingly, both of these independently arising tumors exhibit a loss of chromosome 5. Rat chromosome 5 is syntenic to the major portion of human chromosome 9 (p23-qter). Loss of chromosome 9 is a cytogenetic trait of human superficial TCC, hence the RBT model is also in cytogenetic respect similar to human TCC. Two independently arising rat tumor lines that initially resemble superficial TCC both phenotypically and cytogenetically are described. Upon serial transplantation both lines progressed to a more aggressive tumor, albeit to a different extent (highly vs moderately metastatic). Thus this model system may be helpful in the identification of specific markers associated with the progression of superficial bladder cancer.