Establishment of criteria and technique for molecular genetical diagnosis of urothelial cancer

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We have reported the losses of heterozygosity on chromosome 9 and 17 are clinically important and now we try to examine several molecular markers to apply for molecular genetic diagnosis.P53 is known as a target gene of loss of heterozygosity of chromosome 17 and the mutation of it is in relation to pathological features. This study has proved p53 mutation may be a clinical marker to predict whether the urothelial cancer will progress to be an invasive cancer and has no relation with radiosensitivity.MTS1 and MTS2, those are located on chromosome 9, are tumor supressor genes. This study has proved homozygous deletion or point mutation of these genes often occured in urothelial cancers but has not obvious relation with clinical features which must be proved with further study.Otherwise decrease of E-cadherin, which is one of adhesion molecule expressed in urothelium, is often observed and is in relation to clinical and pathological features.Multiple drug resistance genes such as MDR1, MRP,topo II and GST-pai are clinically important because they are considered to have a relation with drug sensitivity, but no abnormal expression is observed in urothelial cancers.And then we try to develop molecular genetic technique for diagnosis using p53 as a molecular marker.1st, we have modified MASA,that is mutant allele-specific amplification, to avoid false positive and have suceeded to detect cancer cell in urine sediment. And next using short term culture of urine sediment, this study has proved immunocytochemical staining can detect p53 mutation of primary tumor. This may be a powerful method to know malignancy of urothelial cancer.