16q heterozygosity loss in Wilms' tumour in children and its clinical importance

Introduction: The loss of heterozygosity (LOH) of 16q is a structural chang e detected in about 20-30% of Wilms tumour cases. Aberrations which result in deletion of 16q are also found in breast cancer, prostate cancer and liv er cancer, where they are connected with a worse prognosis. The hypothesis of a bad prognosis in nephroblastomas with LOH 16q was first formulated by scientists from NWTS (National Wilms Tumor Study) on the basis of 232 cases of Wilms' tumour. However, SIOP studies (International Society of Paediatr ic Oncology) which included 25 cases of Wilms' tumour, did not show any cli nico-pathological correlations with LOH 16q. Therefore, we aimed to evaluat e the importance of LOH 16q in relation to clinico-pathological factors in a group of children, treated according to the SIOP criteria. Aims: The aim of this work was to evaluate the frequency of LOH 16q in spor adic unilateral Wilms' tumour and to study the relationship between LOH 16q and selected patho-clinical parameters. The study comprised 66 children (3 1 girls and 35 boys) aged from 2 days to 13 years. Methods: LOH 16q was studied by the examination of polymorphism of marker s equences in the region 16q24. DNA was isolated from paraffin sections of ti ssue for routine microscopic examination by the microdissection method. The method of study involved the amplification of polymorphic sequences from t he 16q24 region by polymerase chain reaction (PCR) and separation of the pr oducts of amplification by polyacrylamide gel electrophoresis. The results were the subject of statistical analysis in relation to gender, age of chil d at first diagnosis, stage of clinical advancement and histological type o f tumour. The connection between LOH 16q and recurrences, metastases and de ath, and failure free survival and absolute survival of children followed-u p for over 24 months after nephrectomy were studied. Results: The study revealed a lack of correlation between LOH 16q and gende r, however LOH 16q was more frequent in children with Wilms' tumour aged >2 4 months, P < 0.05. Also, LOH 16q was more frequent in tumours classified a s clinical stage (CS) II or III than in CS I, P < 0.05, but there were no d ifferences in the occurrence of LOH 16q in tumours classified as CS II and CS III. We have found no correlation between LOH 16q and the histological t ype of tumour. However, LOH 16q has been found three times as frequently in tumours from children who died than in tumours of children who survived, P < 0.0024. (C) 2000 Harcourt Publishers Ltd.