膀胱癌における癌抑制遺伝子p53およびRbのヘテロ接合性の消失(LOH)の解析

: Loss of heterozygosity (LOH) at the p53 and Rb genes, and its clinical correlations were examined in 58 urinary bladder carcinomas. DNA was extracted from formalin-fixed, paraffin-embedded tissues, and amplified by polymerase chain reaction (PCR). The LOH at p53 was examined by restriction fragment length polymorphism (RFLP), and the LOH at Rb by single-strand conformation polymorphism (SSCP). Among patients with urinary bladder carcinoma, 60.3% (35/58 patients) showed heterozygosity at p53 and LOH was detected in carcinoma in 60.0% (21/35), i.e., LOH in 61.9% (13/21) of superficial (< or = pT1) and in 57.1% (8/14) of muscular invasive carcinomas. Therefore, LOH at p53 was considered to occur before the beginning of muscular invasion. Except for the patients who died of other causes or were missed during the follow-up, 67.4% (29/43) showed 43.8% (7/16) died of carcinomatosis, but, only 15.4% (2/13) of the patients without p53-LOH died. The 5-year survival rate calculated by the Kaplan-Meier method was 76.9% in patients with heterozygosity at p53, and 25.1% in those with LOH at p53, being significantly lower at p < 0.05 in the former than in the latter. From an analysis of multiple bladder carcinomas, LOH at p53 occurred on the same allele in different tumors of the same bladder, suggesting the monoclonal origin of each tumor of multiple bladder carcinomas. On the other hand, 51.7% (30/58) of patients showed heterozygosity at Rb, and LOH was detected in 16.7% (5/30) of them, i.e., 6.3% (1/16) in superficial carcinoma and 28.6% (4/14) in muscular invasive carcinoma.