Responsiveness of chemotherapy based on the histological type and Wilms' tumor suppressor gene mutation in bilateral Wilms' tumor

To clarify a characteristic of bilateral Wilms' tumor (WT), we examined the clinical and histological features, chemotherapy response and mutations in Wilms' tumor suppressor gene (WT1) in five patients. Deoxyribonucleic acid was extracted from peripheral lymphocytes and tumor samples, and direct DNA sequencing was performed to detect WT1 mutations. Paraffin sections were stained with H&E for histological review and immunostained with anti-WT1, anti-Ki-67, anti-S-100 protein and antimyogenin antibodies. In contrast to the single case of epithelial-type WT, the other four cases were fetal rhabdomyomatous nephroblastoma (FRN) or contained a premature skeletal muscle component and appeared to be resistant to chemotherapy because there was no reduction in tumor volume. However, after chemotherapy, most of the tumor components changed into mature striated muscle cells, most of which immunostained almost completely negative for Ki-67. All four cases had the same point mutation of WTI. From our results, the histological findings correlated with WT1 mutations in bilateral WT. The tumor volume of FRN did not decrease in response to chemotherapy. It is possible to predict the chemotherapy response by examining bilateral WT for WT1 mutations and the histological characteristics of tumors.