LOSS OF THE RETINOBLASTOMA SUSCEPTIBILITY GENE (RB1) IS A FREQUENT AND EARLY EVENT IN PROSTATIC TUMORIGENESIS

Loss of the RBI gene is an important event in the initiation and progr ession of many tumours. Prostate tissue from 43 patients with prostate cancers and ten with benign prostatic hypertrophy (BPH) were studied for loss of heterozygosity of the RBI gene. Four intragenic polymorphi c loci were studied with two techniques. These were restriction fragme nt length polymorphism (RFLP), Southern blotting and hybridisation wit h the p123m1.8 and p68RS2.0 probes (to introns 1 and 17 respectively) and also the polymerase chain reaction (PCR) to amplify loci within in trons 17 and 20. Protein product (pRB) expression was determined by im munohistochemistry using the NCL-RB antibody in nine patients with can cer and four patients with BPH. Loss of heterozygosity was found in 24 out of 40 (60%) informative patients with cancer. Loss of RB1 occurre d with a similar frequency in early-stage and low-grade cancers as in more advanced cancers. Loss of RBI was also found in one patient with BPH. Expression of pRB was completely absent from seven cancers and ma rkedly reduced in the other two, while nuclear pRB staining was always present in areas of BPH, whether alongside cancer-containing tissue o r with BPH alone. We conclude that loss of RB1 is an early event in pr ostatic tumorigenesis.