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BACKGROUND: It has long been discussed whether HCG secreting germinomas are more malignant than pure germinomas. The Japanese study group insists of no difference in survival between two kinds of germinomas, whereas the European and American study groups put HCG germinomas into the high risk group. In order to solve the question, we analyzed the treatment results, the titer of a small amount of HCG-β in the cerebrospinal fluid (CSF), and the expression of HCGβ mRNA in germinoma cells. METHODS: (1) We selected 80 germinoma patients with or without HCG secretion for PFS analysis who were treated by proper radiation volume for their tumors developing in/around the third ventricle in the Japanese prospective study. (2) The initial serum and CSF samples were measured for HCG-β with the ultrasensitive technique to detect picogram levels of HCG-β in 36 histologically confirmed germinomas. (3) The expression of HCGβ mRNA was analyzed by qPCR in 76 germ cell tumors. RESULTS: (1) There was no significant difference in 15 year PFS between pure germinomas (93.1%, n = 61) and HCG-germinomas (80.7%, n = 19) in the Japanese prospective study. (2) In 36 germinomas examined, the HCG-β was detectable in both serum and CSF. The serum levels were 3.1–5851 pg/mL (median 44.8), and the CSF levels were 13–13116.3 pg/mL (median 119.5). (3) Most of the germ cell tumors expressed HCG-β mRNA in higher degrees compared with the normal brain tissue (comparative ratio to brain: 0.46 - 7.6 × 107). The expression of HCG-β mRNA in germinomas was highly variable, ranging from 72.6 - 2.1 × 105 to below the brain (0.46 - 1.4 × 103), and the differences of the expression among cases were linear, and not bimodal, suggesting no clear cut-off titer. CONCLUSIONS: These results suggest that all germinomas can produce HCG-β and fall into the same category in terms of HCG-β productivity. Based on this theory, all germinoma patients should be treated with the same protocol. SECONDARY CATEGORY: Pediatrics.

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