DNA Ploidy analysis in wilms' Tumor, wilms' Tumor variants and nephroblastomatosis

Abstract

Wilms' tumor is a complex embryonic tumor of the kidney occurring most commonly in children under 10 years of age. Stage and histology are currently considered to be the best predictors of outcome. In approximately 25% of cases Wilms' tumor is associated with nephroblastomatosis in the same or contralateral kidney. Much less common are cystic variants of Wilms' tumor; cystic nephroma (CN), also known as multilocular cyst of the kidney and cystic partially differentiated nephroblastoma (CPDN). In general these cystic variants have an excellent prognosis when treated by nephrectomy alone although CPDN may rarely be locally aggressive. Since methods for analysing the DNA content of nuclei extracted from paraffin blocks have become available, flow cytometry has been performed on a range of tumors and has been shown to correlate with outcome. We wished to determine if there was any difference in DNA content between typical favourable histology Wilms' tumor and the less common cystic variants and precursor lesions. Flow cytometry was used to analyse the DNA content of Wilms' (4 cases I, CPDN with Wilms' tumor (1 case), CPDN (1 easel, CN (2 cases) and nephroblastomatosis (1 easel. The 9 cases were processed by a modified Hedley technique. The specimens were stained with propidium iodide and analysed on a Coulter EPICS Profile II flow cytometer using a 488nm air-cooled laser. A minimum of 15000 nuclei were counted in each case. In all cases a diploid DNA content was found. The mean half peak C.V. value for the major peaks was 3.34 and the median half-peak C.V. was 3.22. The S phase fraction varied from 0-19% with a mean of 7.1%. It appears from these preliminary data that DNA ploidy does not distinguish between Wilms' tumor and variants although it is possible that S phase fraction may prove to be of benefit in determining malignant potential. We are currently undertaking a more extensive study to determine if DNA content or S phase fraction can be used to predict treatment failure in favourable histology Wilms' tumor. Wilms' tumor is a complex embryonic tumor of the kidney occurring most commonly in children under 10 years of age. Stage and histology are currently considered to be the best predictors of outcome. In approximately 25% of cases Wilms' tumor is associated with nephroblastomatosis in the same or contralateral kidney. Much less common are cystic variants of Wilms' tumor; cystic nephroma (CN), also known as multilocular cyst of the kidney and cystic partially differentiated nephroblastoma (CPDN). In general these cystic variants have an excellent prognosis when treated by nephrectomy alone although CPDN may rarely be locally aggressive. Since methods for analysing the DNA content of nuclei extracted from paraffin blocks have become available, flow cytometry has been performed on a range of tumors and has been shown to correlate with outcome. We wished to determine if there was any difference in DNA content between typical favourable histology Wilms' tumor and the less common cystic variants and precursor lesions. Flow cytometry was used to analyse the DNA content of Wilms' (4 cases I, CPDN with Wilms' tumor (1 case), CPDN (1 easel, CN (2 cases) and nephroblastomatosis (1 easel. The 9 cases were processed by a modified Hedley technique. The specimens were stained with propidium iodide and analysed on a Coulter EPICS Profile II flow cytometer using a 488nm air-cooled laser. A minimum of 15000 nuclei were counted in each case. In all cases a diploid DNA content was found. The mean half peak C.V. value for the major peaks was 3.34 and the median half-peak C.V. was 3.22. The S phase fraction varied from 0-19% with a mean of 7.1%. It appears from these preliminary data that DNA ploidy does not distinguish between Wilms' tumor and variants although it is possible that S phase fraction may prove to be of benefit in determining malignant potential. We are currently undertaking a more extensive study to determine if DNA content or S phase fraction can be used to predict treatment failure in favourable histology Wilms' tumor.