Loss of heterozygosity at the p53, Rb, DCC and APC tumor suppressor gene loci in human bladder cancer

Purpose: Allelic losses within several tumor suppressor genes have been detected frequently in various types of human cancer. We investigated the roles and possible interactions of the tumor suppressor genes p53, Rb, DCC and APC in bladder cancer. Materials and Methods: Loss of heterozygosity (LOH) of these 4 genes was examined in 45 human bladder cancers by polymerase chain reaction and restriction fragment length polymorphism assay. Results: Of the evaluated cases, LOH was seen at p53 in 38%, at Rb in 22%, at DCC in 36% and at APC in 6% of tumors. Loss of heterozygosity at p53 and Rb was predominantly observed in high grade (grade 3) and/or invasive (T2 or greater) tumors, whereas LOH at DCC was present irrespective of tumor grade and stage. Allelic losses at either p53, Rb, DCC, or APC were seen in 82% of high grade tumors, but in only 21% of low grade (grade 1 and 2) tumors (p <0.005). Similarly, 71% of invasive tumors had LOH at one or more loci compared with 20% of superficial (Ta and T1) tumors (p <0.005). Interestingly, p53-LOH and Rb-LOH were often observed simultaneously in the same tumor. Conclusions: These results suggest that loss of the p53, Rb and/or DCC genes is involved in most of the late and some of the early steps of bladder carcinogenesis.