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 performe d. In the genitourinary tract four kidney and five bladder tumors were found. Two of these bladder tumors, RBT323 and RBT157, are serially t ransplantable. In the fifth transplant generation the RBT323 tumor bec omes metastatic to the lungs in more than 90% of animals. The metastat ic ability of the RBT157 tumor changes from low to intermediate (50% o f the rats have lung metastases) in the fourth passage. Histologically , the initial passages of the RBT323 and 157 tumors are grade II trans itional cell carcinoma (TCC). The histological pattern of the RBT157 t umor remains essentially unchanged, whereas the RBT323 tumor progresse s to a grade III tumor in the third passage. Electron microscopical st udies reveal oblong elliptical and round vesicles lined by an asymmetr ical unit membrane in the tumor cells, which stresses the urothelial o rigin. of the tumors. Immunohistochemically both tumors show expressio n of cytokeratin 5, 7, 8 and 18. The progression of the tumors to a me tastatic 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. Interestingl y, both of these independently arising tumors exhibit a loss of chromo some 5. Rat chromosome 5 is syntenic to the major portion of human chr omosome 9 (p23-qter). Loss of chromosome 9 is a cytogenetic trait of h uman superficial TCC, hence the RBT model is also in cytogenetic respe ct similar to human TCC. Two independently arising rat tumor lines tha t initially resemble superficial TCC both phenotypically and cytogenet ically are described. Upon serial transplantation both lines progresse d to a more aggressive tumor, albeit to a different extent (highly vs moderately metastatic). Thus this model system may be helpful in the i dentification of specific markers associated with the progression of s uperficial bladder cancer.