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Human chorionic gonadotropin is expressed virtually in all intracranial germ cell tumors

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Abstract

Human chorionic gonadotropin (hCG) production has been utilized as a diagnostic marker for germinoma with syncytiotrophoblastic giant cells (STGC) and choriocarcinoma. Elevated hCG in germinoma is considered to predict less favorable prognosis, and an intensive treatment strategy may accordingly be applied. However, there is some evidence that any germinoma may produce hCG to varying extent. We investigated mRNA expression of the hCG β subunit (hCGβ) using real time quantitative polymerase chain reaction in 94 germ cell tumors (GCTs). Most (93.3 %) GCTs showed higher expression levels compared with that of normal brain tissue (1.09 × 100–1.40 × 105 fold). The expression was the highest in GCTs which harbor choriocarcinoma or STGC components. The expression level of hCGβ in germinoma was highly variable (1.09 × 100–5.88 × 104 fold) in linear but not bimodal distribution. hCG concentrations in serum and CSF correlated with gene expression, especially when GCTs with single histological component were analyzed separately. The expression was not significantly associated with recurrence in pure germinoma. These results suggest that the serum/CSF hCG levels may need to be interpreted with caution as most GCTs appear to have the capacity of producing hCG irrespective of their histology. The clinical significance of ubiquitous hCG expression in GCTs needs further investigation.

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References

  1. Shibui S (2014) Report of the brain tumor registry of Japan, 2001–2004

  2. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, Scheithauer BW, Kleihues P (2007) The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 114:97–109

    Article  PubMed Central  PubMed  Google Scholar 

  3. Göbel U, Schneider DT, Calaminus G, Haas RJ, Schmidt P, Harms D (2000) Germ-cell tumors in childhood and adolescence. GPOH MAKEI and the MAHO study groups. Ann Oncol: Off J Eur Soc Med Oncol/ESMO 11:263–271

    Article  Google Scholar 

  4. Inamura T, Nishio S, Ikezaki K, Fukui M (1999) Human chorionic gonadotrophin in CSF, not serum, predicts outcome in germinoma. J Neurol Neurosurg Psychiat 66:654–657

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. Utsuki S, Kawano N, Oka H, Tanaka T, Suwa T, Fujii K (1999) Cerebral germinoma with syncytiotrophoblastic giant cells: feasibility of predicting prognosis using the serum hCG level. Acta Neurochir 141:975 discussion 977-978

    Article  CAS  PubMed  Google Scholar 

  6. Ogino H, Shibamoto Y, Takanaka T, Suzuki K, Ishihara S, Yamada T, Sugie C, Nomoto Y, Mimura M (2005) CNS germinoma with elevated serum human chorionic gonadotropin level: clinical characteristics and treatment outcome. Int J Radiat Oncol Biol Phys 62:803–808. doi:10.1016/j.ijrobp.2004.10.026

    Article  CAS  PubMed  Google Scholar 

  7. Shibamoto Y, Takahashi M, Sasai K (1997) Prognosis of intracranial germinoma with syncytiotrophoblastic giant cells treated by radiation therapy. Int J Radiat Oncol Biol Phys 37:505–510

    Article  CAS  PubMed  Google Scholar 

  8. Matsutani M, Sano K, Takakura K, Fujimaki T, Nakamura O, Funata N, Seto T (1997) Primary intracranial germ cell tumors: a clinical analysis of 153 histologically verified cases. J Neurosurg 86:446–455. doi:10.3171/jns.1997.86.3.0446

    Article  CAS  PubMed  Google Scholar 

  9. Sawamura Y, Ikeda J, Shirato H, Tada M, Abe H (1998) Germ cell tumours of the central nervous system: treatment consideration based on 111 cases and their long-term clinical outcomes. Eur J Cancer 34:104–110

    Article  CAS  PubMed  Google Scholar 

  10. Fujimaki T, Matsutani M, Nishikawa R, Mishima K, Suzuki T, Katakami H (2011) All germinomas are capable of producing hCG-beta and might be treated in the same protocol. Neuro-oncology 13:I13

    Google Scholar 

  11. Katakami H, Hashida S, Yamaguchi H, Yazawa S, Nakano S, Wakisaka S, Matsutani M (2003) Diagnosis and follow-up of CNS germ cell tumors using an ultrasensitive assay of HCG-beta. Horm Clin 51:196–206

    Google Scholar 

  12. Utsuki S, Oka H, Tanizaki Y, Kondo K, Kawano N, Fujii K (2005) Pathological features of intracranial germinomas with reference to fibrous tissue and granulomatous change. Brain Tumor Pathol 22:9–13. doi:10.1007/s10014-004-0171-0

    Article  PubMed  Google Scholar 

  13. Zeng N, Liu L, McCabe MG, Jones DT, Ichimura K, Collins VP (2009) Real-time quantitative polymerase chain reaction (qPCR) analysis with fluorescence resonance energy transfer (FRET) probes reveals differential expression of the four ERBB4 juxtamembrane region variants between medulloblastoma and pilocytic astrocytoma. Neuropathol Appl Neurobiol 35:353–366. doi:10.1111/j.1365-2990.2008.01001.x

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Fukushima S, Otsuka A, Suzuki T, Yanagisawa T, Mishima K, Mukasa A, Saito N, Kumabe T, Kanamori M, Tominaga T, Narita Y, Shibui S, Kato M, Shibata T, Matsutani M, Nishikawa R, Ichimura K (2014) Mutually exclusive mutations of KIT and RAS are associated with KIT mRNA expression and chromosomal instability in primary intracranial pure germinomas. Acta Neuropathol. doi:10.1007/s00401-014-1247-5

    PubMed  Google Scholar 

  15. Allred DC, Harvey JM, Berardo M, Clark GM (1998) Prognostic and predictive factors in breast cancer by immunohistochemical analysis. Modern Pathol: An Off J United States and Can Acad of Pathol Inc 11:155–168

    CAS  Google Scholar 

  16. Mohsin SK, Weiss H, Havighurst T, Clark GM, Berardo M, le Roanh D, To TV, Qian Z, Love RR, Allred DC (2004) Progesterone receptor by immunohistochemistry and clinical outcome in breast cancer: a validation study. Modern Pathol: An Off J United States and Can Acad Pathol Inc 17:1545–1554. doi:10.1038/modpathol.3800229

    Article  CAS  Google Scholar 

  17. Bjornsson J, Scheithauer BW, Okazaki H, Leech RW (1985) Intracranial germ cell tumors: pathobiological and immunohistochemical aspects of 70 cases. J Neuropathol Exp Neurol 44:32–46

    Article  CAS  PubMed  Google Scholar 

  18. Ikura Y, Sasaki M, Ohgami M, Ikebe T, Gotoh K, Bettoh H, Sakurai M (1996) Mixed germ-cell tumor of the brain. Pathologic study of six autopsy cases. Pathol Res Ractice 192:595–603. doi:10.1016/S0344-0338(96)80111-7

    Article  CAS  Google Scholar 

  19. Tamaki N, Lin T, Shirataki K, Hosoda K, Kurata H, Matsumoto S, Ito H (1990) Germ cell tumors of the thalamus and the basal ganglia. Child’s Nerv Syst: ChNS: Off J Int Soc Pediatr Neurosurg 6:3–7

    Article  CAS  Google Scholar 

  20. Teilum G (1965) Classification of endodermal sinus tumour (mesoblatoma vitellinum) and so-called “embryonal carcinoma” of the ovary. Acta Pathologica et Microbiologica Scandinavica 64:407–429

    CAS  PubMed  Google Scholar 

  21. Sano K (1999) Pathogenesis of intracranial germ cell tumors reconsidered. J Neurosurg 90:258–264. doi:10.3171/jns.1999.90.2.0258

    Article  CAS  PubMed  Google Scholar 

  22. Yamagami T, Handa H, Yamashita J, Okumura T, Paine J, Haebara H, Furukawa F (1987) An immunohistochemical study of intracranial germ cell tumours. Acta Neurochir 86:33–41

    Article  CAS  PubMed  Google Scholar 

  23. Tan C, Scotting PJ (2013) Stem cell research points the way to the cell of origin for intracranial germ cell tumours. J Pathol 229:4–11. doi:10.1002/path.4098

    Article  CAS  PubMed  Google Scholar 

  24. Wong JM, Chi SN, Marcus KJ, Levine BS, Ullrich NJ, MacDonald S, Lechpammer M, Goumnerova LC (2010) Germinoma with malignant transformation to nongerminomatous germ cell tumor. J Neurosurg Pediatr 6:295–298. doi:10.3171/2010.6.PEDS09541

    Article  PubMed  Google Scholar 

  25. Mostofi FK (1973) Tumors of the male genital system. Armed Forces Institute of Pathology, Washington, D.C.

    Google Scholar 

  26. Madersbacher S, Kratzik C, Gerth R, Dirnhofer S, Berger P (1994) Human chorionic gonadotropin (hCG) and its free subunits in hydrocele fluids and neoplastic tissue of testicular cancer patients: insights into the in vivo hCG-secretion pattern. Cancer Res 54:5096–5100

    CAS  PubMed  Google Scholar 

  27. Irie N, Weinberger L, Tang WW, Kobayashi T, Viukov S, Manor YS, Dietmann S, Hanna JH, Surani MA (2015) SOX17 is a critical specifier of human primordial germ cell fate. Cell 160:253–268. doi:10.1016/j.cell.2014.12.013

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Louhimo J, Carpelan-Holmstrom M, Alfthan H, Stenman UH, Jarvinen HJ, Haglund C (2002) Serum HCG beta, CA 72-4 and CEA are independent prognostic factors in colorectal cancer. Int J Cancer 101:545–548. doi:10.1002/ijc.90009

    Article  PubMed  Google Scholar 

  29. Vartiainen J, Lassus H, Lehtovirta P, Finne P, Alfthan H, Butzow R, Stenman UH (2008) Combination of serum hCG beta and p53 tissue expression defines distinct subgroups of serous ovarian carcinoma. Int J Cancer 122:2125–2129. doi:10.1002/ijc.23322

    Article  CAS  PubMed  Google Scholar 

  30. Cole LA (2010) Biological functions of hCG and hCG-related molecules. Reprod Biol Endocrinol: RB&E 8:102. doi:10.1186/1477-7827-8-102

    Article  Google Scholar 

  31. Cole LA, Butler S (2012) Hyperglycosylated hCG, hCGbeta and Hyperglycosylated hCGbeta: interchangeable cancer promoters. Mol Cell Endocrinol 349:232–238. doi:10.1016/j.mce.2011.10.029

    Article  CAS  PubMed  Google Scholar 

  32. Lempiainen A, Sankila A, Hotakainen K, Haglund C, Blomqvist C, Stenman UH (2014) Expression of human chorionic gonadotropin in testicular germ cell tumors. Urol Oncol 32:727–734. doi:10.1016/j.urolonc.2013.11.007

    Article  CAS  PubMed  Google Scholar 

  33. Oosterhuis JW, Stoop H, Honecker F, Looijenga LH (2007) Why human extragonadal germ cell tumours occur in the midline of the body: old concepts, new perspectives. Int J Androl 30:256. discussion 263-254 doi:10.1111/j.1365-2605.2007.00793.x

    Article  PubMed  Google Scholar 

  34. Jennings MT, Gelman R, Hochberg F (1985) Intracranial germ-cell tumors: natural history and pathogenesis. J Neurosurg 63:155–167. doi:10.3171/jns.1985.63.2.0155

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by a research program of the Project for Development of Innovative Research on Cancer Therapeutics (P-Direct) Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan. We thank Dr Hideki Katakami for sharing valuable data and inspiring the project, and Dr Sylvia Kocialkowski for critical reading of the manuscript.

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The authors declare that we have no conflict of interest.

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Correspondence to Koichi Ichimura.

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On behalf of the Intracranial Germ Cell Tumor Genome Analysis Consortium (the iGCT Consortium).

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Takami, H., Fukushima, S., Fukuoka, K. et al. Human chorionic gonadotropin is expressed virtually in all intracranial germ cell tumors. J Neurooncol 124, 23–32 (2015). https://doi.org/10.1007/s11060-015-1809-y

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  • DOI: https://doi.org/10.1007/s11060-015-1809-y

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