KIT gene mutation and amplification in dysgerminoma of the ovary

BACKGROUND: Dysgerminoma, the ovarian counterpart of seminoma, is the most common type of malignant ovarian germ cell tumor. The role of KIT mutation and amplification in the development of dysgerminoma is not currently established. The purpose of this study was to analyze alterations of the KIT gene in a large series of dysgerminomas and correlate the findings with clinicopathological parameters. METHODS: Dysgerminoma cells from 22 patients were analyzed for KIT mutations at exon 17 codon 816. KIT amplification and chromosome 12p anomalies were investigated by way of dual color fluorescence in situ hybridization. KIT protein expression was also examined by way of immunohistochemistry. RESULTS: KIT exon 17 codon 816 mutations and KIT amplification were each detected in 6 cases of dysgerminoma (27%); however, there was no correlation between these 2 factors. KIT expression was detected in 87% of dysgerminomas. The KIT mutation was associated with advanced pathological stage (P <.05), and KIT amplification was associated with elevated KIT protein expression (P <.05). Chromosome 12p anomalies were found in 82% of the dysgerminomas and did not correlate with KIT abnormalities. CONCLUSIONS: KIT mutations occur in approximately one-third of cases of dysgerminomas and are associated with advanced stage at presentation. KIT is a potential therapeutic target for those dysgerminomas that have the mutation.