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Erschienen in: Journal of Neuro-Oncology 1/2015

01.08.2015 | Laboratory Investigation

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

verfasst von: Hirokazu Takami, Shintaro Fukushima, Kohei Fukuoka, Tomonari Suzuki, Takaaki Yanagisawa, Yuko Matsushita, Taishi Nakamura, Hideyuki Arita, Akitake Mukasa, Nobuhito Saito, Masayuki Kanamori, Toshihiro Kumabe, Teiji Tominaga, Keiichi Kobayashi, Motoo Nagane, Toshihiko Iuchi, Kaoru Tamura, Taketoshi Maehara, Kazuhiko Sugiyama, Mitsutoshi Nakada, Yonehiro Kanemura, Masahiro Nonaka, Kiyotaka Yokogami, Hideo Takeshima, Yoshitaka Narita, Soichiro Shibui, Yoichi Nakazato, Ryo Nishikawa, Koichi Ichimura, Masao Matsutani

Erschienen in: Journal of Neuro-Oncology | Ausgabe 1/2015

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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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Literatur
1.
Zurück zum Zitat Shibui S (2014) Report of the brain tumor registry of Japan, 2001–2004 Shibui S (2014) Report of the brain tumor registry of Japan, 2001–2004
2.
Zurück zum Zitat 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 114:97–109PubMedCentralPubMedCrossRef 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 114:97–109PubMedCentralPubMedCrossRef
3.
Zurück zum Zitat 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 11:263–271CrossRef 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 11:263–271CrossRef
4.
Zurück zum Zitat Inamura T, Nishio S, Ikezaki K, Fukui M (1999) Human chorionic gonadotrophin in CSF, not serum, predicts outcome in germinoma. J Neurol Neurosurg Psychiat 66:654–657PubMedCentralPubMedCrossRef Inamura T, Nishio S, Ikezaki K, Fukui M (1999) Human chorionic gonadotrophin in CSF, not serum, predicts outcome in germinoma. J Neurol Neurosurg Psychiat 66:654–657PubMedCentralPubMedCrossRef
5.
Zurück zum Zitat 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 977-978PubMedCrossRef 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 977-978PubMedCrossRef
6.
Zurück zum Zitat 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 PubMedCrossRef 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 PubMedCrossRef
7.
Zurück zum Zitat 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 37:505–510PubMedCrossRef 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 37:505–510PubMedCrossRef
9.
Zurück zum Zitat 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 34:104–110PubMedCrossRef 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 34:104–110PubMedCrossRef
10.
Zurück zum Zitat 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 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
11.
Zurück zum Zitat 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 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
12.
Zurück zum Zitat 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 PubMedCrossRef 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 PubMedCrossRef
13.
Zurück zum Zitat 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 PubMedCentralPubMedCrossRef 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 PubMedCentralPubMedCrossRef
14.
Zurück zum Zitat 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 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
15.
Zurück zum Zitat 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 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
16.
Zurück zum Zitat 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 CrossRef 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 CrossRef
17.
Zurück zum Zitat Bjornsson J, Scheithauer BW, Okazaki H, Leech RW (1985) Intracranial germ cell tumors: pathobiological and immunohistochemical aspects of 70 cases. J Neuropathol Exp Neurol 44:32–46PubMedCrossRef Bjornsson J, Scheithauer BW, Okazaki H, Leech RW (1985) Intracranial germ cell tumors: pathobiological and immunohistochemical aspects of 70 cases. J Neuropathol Exp Neurol 44:32–46PubMedCrossRef
18.
19.
Zurück zum Zitat 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 6:3–7CrossRef 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 6:3–7CrossRef
20.
Zurück zum Zitat Teilum G (1965) Classification of endodermal sinus tumour (mesoblatoma vitellinum) and so-called “embryonal carcinoma” of the ovary. Acta Pathologica et Microbiologica Scandinavica 64:407–429PubMed Teilum G (1965) Classification of endodermal sinus tumour (mesoblatoma vitellinum) and so-called “embryonal carcinoma” of the ovary. Acta Pathologica et Microbiologica Scandinavica 64:407–429PubMed
22.
Zurück zum Zitat 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 86:33–41PubMedCrossRef 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 86:33–41PubMedCrossRef
24.
Zurück zum Zitat 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 PubMedCrossRef 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 PubMedCrossRef
25.
Zurück zum Zitat Mostofi FK (1973) Tumors of the male genital system. Armed Forces Institute of Pathology, Washington, D.C. Mostofi FK (1973) Tumors of the male genital system. Armed Forces Institute of Pathology, Washington, D.C.
26.
Zurück zum Zitat 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 54:5096–5100PubMed 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 54:5096–5100PubMed
28.
Zurück zum Zitat 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 PubMedCrossRef 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 PubMedCrossRef
29.
Zurück zum Zitat 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 PubMedCrossRef 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 PubMedCrossRef
Metadaten
Titel
Human chorionic gonadotropin is expressed virtually in all intracranial germ cell tumors
verfasst von
Hirokazu Takami
Shintaro Fukushima
Kohei Fukuoka
Tomonari Suzuki
Takaaki Yanagisawa
Yuko Matsushita
Taishi Nakamura
Hideyuki Arita
Akitake Mukasa
Nobuhito Saito
Masayuki Kanamori
Toshihiro Kumabe
Teiji Tominaga
Keiichi Kobayashi
Motoo Nagane
Toshihiko Iuchi
Kaoru Tamura
Taketoshi Maehara
Kazuhiko Sugiyama
Mitsutoshi Nakada
Yonehiro Kanemura
Masahiro Nonaka
Kiyotaka Yokogami
Hideo Takeshima
Yoshitaka Narita
Soichiro Shibui
Yoichi Nakazato
Ryo Nishikawa
Koichi Ichimura
Masao Matsutani
Publikationsdatum
01.08.2015
Verlag
Springer US
Erschienen in
Journal of Neuro-Oncology / Ausgabe 1/2015
Print ISSN: 0167-594X
Elektronische ISSN: 1573-7373
DOI
https://doi.org/10.1007/s11060-015-1809-y

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