Abstracts for the Second International Symposium on Central Nervous System Germ Cell Tumors

The purpose of this study is to further characterize the immunophenotype of CNS germinomas with emphasis on the expression of CD117 (c-kit) in relation to possible mutations of the c-kit gene. Biopsy material from 20 CNS germinoma cases was studied immunohistochemically. In 10 cases, archived frozen tumor tissue was available for c-kit proto-oncogene mutation analysis. DNA extracted from regions with 80% tumor density underwent whole genome amplifi cation prior to mutation analysis. In one additional case, mutation analysis was performed on paraffi n-embedded tissue. Forward and reverse sequencing were performed on c-kit's exons 9, 11, 13, and 17. The neuroanatomical distribution of tumors is as follows: 10 pineal, six suprasellar, two thalamic, one basal ganglia, and one in the posterior third ventricle. There were 15 males and fi ve females, with an age average of 13.25 years and an age range of 7 to 17 years. The immunohistochemical profi le revealed strong positive staining for PLAP and CD117 in 100% of cases. The latter was always diffuse and stronger than PLAP. This difference was more accentuated in tissue frozen for intraoperative consultation and subsequently fi xed in formalin and processed routinely. HCG showed a weak diffuse cytoplasmic staining with few scattered strongly stained cells. AFP, CEA, and CD30 were consistently negative. Staining for vimentin and keratin reveal few scattered cells showing focal cytoplasmic staining. Molecular analysis for c-kit mutations showed 1/11 tumors with exon 17 (N822Y) mutation. This mutation represents gain-of-function mutation. We conclude that CD117 is a reliable immunohistochemical marker for germinomas. No relation between immunophenotype and mutations analysis was identifi ed. The 9% c-kit mutation rate in our study is consistent with previous reports of low frequency of c-kit mutations in germinomas.