Skip to main content
Top
Published in: Journal of Neuro-Oncology 3/2013

01-12-2013 | Laboratory Investigation

Correlation between the prognostic value and the expression of the stem cell marker CD133 and isocitrate dehydrogenase1 in glioblastomas

Authors: Jung Ha Shin, Youn Soo Lee, Yong-Kil Hong, Chang Suk Kang

Published in: Journal of Neuro-Oncology | Issue 3/2013

Login to get access

Abstract

Cancer stem cells are thought to be responsible for tumor recurrence and resistance in glioblastomas. An isocitrate dehydrogenase1 (IDH1) mutation, affecting codon132 of the isocitrate dehydrogenase1 gene, has prognostic significance in glioblastomas. We investigated whether stem cell marker expression [CD133, CD34, and vascular endothelial growth factor (VEGF)] and IDH1 mutation correlate with clinical factors and prognosis in glioblastoma. CD133, CD34, and VEGF expression was evaluated by immunohistochemistry in 67 cases of glioblastoma identified between 2005 and 2012. IDH1 mutation was assessed by immunohistochemistry, peptide-nucleic-acid mediated PCR clamping, and direct gene sequencing. Diffuse CD133 expression was detected in 12 (17.9 %) cases and was associated with poor overall survival (OS) (P = 0.010) and progression-free survival (P = 0.017). CD34 and VEGF expression were not associated with prognosis in these samples. IDH1 mutation was detected in ten (14.9 %) cases. Eight were clinically secondary tumors and two were primary tumors (P < 0.001); the mean age of the secondary tumor patients was significantly younger (P = 0.001, 41.20 vs. 59.14). IDH1-positive patients had longer OS than IDH1-negative patients (25.78 vs. 22.95 months), but this difference was not significant. In addition, IDH1 and CD34 expression showed a negative correlation (P = 0.024). Multivariate analysis showed that age, extent of surgery, and diffuse CD133 expression correlated with OS. CD133 may be a survival marker for glioblastoma. Further characterization of CD133, IDH1, and vascular markers in glioblastoma may help identify new therapeutic targets.
Appendix
Available only for authorised users
Literature
2.
go back to reference Bao S, Wu Q, McLendon RE, McLendon RE, Hao Y, Shi Q, Hjelmeland AB, Dewhirst MW, Bigner DD, Rich JN (2006) Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 444:756–760PubMedCrossRef Bao S, Wu Q, McLendon RE, McLendon RE, Hao Y, Shi Q, Hjelmeland AB, Dewhirst MW, Bigner DD, Rich JN (2006) Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 444:756–760PubMedCrossRef
4.
go back to reference Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, Henkelman RM, Cusimano MD, Dirks PB (2004) Identification of human brain tumour initiating cells. Nature 432:396–401PubMedCrossRef Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, Henkelman RM, Cusimano MD, Dirks PB (2004) Identification of human brain tumour initiating cells. Nature 432:396–401PubMedCrossRef
5.
go back to reference Zeppernick F, Ahmadi R, Campos B, Dictus C, Helmke BM, Becker N, Lichter P, Unterberg A, Radlwimmer B, Herold-Mende CC (2008) Stem cell marker CD133 affects clinical outcome in glioma patients. Clin Cancer Res 14:123–129PubMedCrossRef Zeppernick F, Ahmadi R, Campos B, Dictus C, Helmke BM, Becker N, Lichter P, Unterberg A, Radlwimmer B, Herold-Mende CC (2008) Stem cell marker CD133 affects clinical outcome in glioma patients. Clin Cancer Res 14:123–129PubMedCrossRef
6.
go back to reference Pallini R, Ricci-Vitiani L, Banna GL, Signore M, Lombardi D, Todaro M, Stassi G, Martini M, Maira G, Larocca LM, Maria RD (2008) Cancer stem cell analysis and clinical outcome in patients with glioblastoma multiforme. Clin Cancer Res 14:8205–8212PubMedCrossRef Pallini R, Ricci-Vitiani L, Banna GL, Signore M, Lombardi D, Todaro M, Stassi G, Martini M, Maira G, Larocca LM, Maria RD (2008) Cancer stem cell analysis and clinical outcome in patients with glioblastoma multiforme. Clin Cancer Res 14:8205–8212PubMedCrossRef
7.
go back to reference Thon N, Damianoff K, Hegermann J, Gras S, Krebs B, Schnell O, Tonn JC, Goldbrunner R (2010) Presence of pluripotent CD133+ cells correlates with malignancy of gliomas. Mol Cell Neurosci 43:51–59PubMedCrossRef Thon N, Damianoff K, Hegermann J, Gras S, Krebs B, Schnell O, Tonn JC, Goldbrunner R (2010) Presence of pluripotent CD133+ cells correlates with malignancy of gliomas. Mol Cell Neurosci 43:51–59PubMedCrossRef
8.
go back to reference Eramo A, Ricci-Vitiani L, Zeuner A, Pallini R, Lotti F, Sette G, Pilozzi E, Larocca LM, Peschle C, Maria RD (2006) Chemotherapy resistance of glioblastoma stem cells. Cell Death Differ 13:1238–1241PubMedCrossRef Eramo A, Ricci-Vitiani L, Zeuner A, Pallini R, Lotti F, Sette G, Pilozzi E, Larocca LM, Peschle C, Maria RD (2006) Chemotherapy resistance of glioblastoma stem cells. Cell Death Differ 13:1238–1241PubMedCrossRef
9.
go back to reference He H, Niu CS, Li MY (2012) Correlation between glioblastoma stem-like cells and tumor vascularization. Oncol Rep 27:45–50PubMed He H, Niu CS, Li MY (2012) Correlation between glioblastoma stem-like cells and tumor vascularization. Oncol Rep 27:45–50PubMed
10.
go back to reference Garcia JL, Perez-Caro M, Gomez-Moreta JA, Gonzalez F, Ortiz J, Blanco O, Sancho M, Hernandez-Rivas JM, Gonzalez-Sarmiento R, Sanchez-Martin M (2010) Molecular analysis of ex vivo CD133+ GBM cells revealed a common invasive and angiogenic profile but different proliferative signatures among high grade gliomas. BMC Cancer 10:454–469PubMedCrossRef Garcia JL, Perez-Caro M, Gomez-Moreta JA, Gonzalez F, Ortiz J, Blanco O, Sancho M, Hernandez-Rivas JM, Gonzalez-Sarmiento R, Sanchez-Martin M (2010) Molecular analysis of ex vivo CD133+ GBM cells revealed a common invasive and angiogenic profile but different proliferative signatures among high grade gliomas. BMC Cancer 10:454–469PubMedCrossRef
11.
go back to reference Gilbertson RJ, Rich JN (2007) Making a tumour’s bed: glioblastoma stem cells and the vascular niche. Nat Rev Cancer 7:733–736PubMedCrossRef Gilbertson RJ, Rich JN (2007) Making a tumour’s bed: glioblastoma stem cells and the vascular niche. Nat Rev Cancer 7:733–736PubMedCrossRef
12.
go back to reference Fischer I, Cunliffe CH, Bollo RJ, Raza BS, Monoky D, Chiriboga L, Parker EC, Golfinos JG, Kelly PJ, Knopp EA, Gruber ML, Zagzag D, Narayana A (2008) High-grade glioma before and after treatment with radiation and Avastin: initial observations. Neuro-Oncology 10:700–708PubMedCrossRef Fischer I, Cunliffe CH, Bollo RJ, Raza BS, Monoky D, Chiriboga L, Parker EC, Golfinos JG, Kelly PJ, Knopp EA, Gruber ML, Zagzag D, Narayana A (2008) High-grade glioma before and after treatment with radiation and Avastin: initial observations. Neuro-Oncology 10:700–708PubMedCrossRef
13.
go back to reference Takano S, Tian W, Matsuda M, Yamamoto T, Ishikawa E, Kaneko MK, Uamazaki K, Kato Y, Matsumura A (2011) Detection of IDH1 mutation in human gliomas: comparison of immunohistochemistry and sequencing. Brain Tumor Pathol 28:115–123PubMedCrossRef Takano S, Tian W, Matsuda M, Yamamoto T, Ishikawa E, Kaneko MK, Uamazaki K, Kato Y, Matsumura A (2011) Detection of IDH1 mutation in human gliomas: comparison of immunohistochemistry and sequencing. Brain Tumor Pathol 28:115–123PubMedCrossRef
14.
go back to reference Figueroa ME, Abdel-Wahab O, Lu C, Ward PS, Patel J, Shih A, Li Y, Bhagwat N, Vasanthakumar A, Fernandez HF, Tallman MS, Sun Z, Eolniak K, Peeters JK, Liu W, Choe SE, Fantin VR, Paietta E, Lowenberg B, Licht JD, Godley LA, Delwel R, Valk PJM, Thompson CB, Levine RL, Melnick A (2010) Leukemic IDH1 and IDH2 Mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation. Cancer Cell 18:553–567PubMedCrossRef Figueroa ME, Abdel-Wahab O, Lu C, Ward PS, Patel J, Shih A, Li Y, Bhagwat N, Vasanthakumar A, Fernandez HF, Tallman MS, Sun Z, Eolniak K, Peeters JK, Liu W, Choe SE, Fantin VR, Paietta E, Lowenberg B, Licht JD, Godley LA, Delwel R, Valk PJM, Thompson CB, Levine RL, Melnick A (2010) Leukemic IDH1 and IDH2 Mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation. Cancer Cell 18:553–567PubMedCrossRef
15.
go back to reference Wu Y, Wu PY (2009) CD133 as a marker for cancer stem cells: progresses and concerns. Stem Cells Dev 18:1127–1134PubMedCrossRef Wu Y, Wu PY (2009) CD133 as a marker for cancer stem cells: progresses and concerns. Stem Cells Dev 18:1127–1134PubMedCrossRef
16.
go back to reference Pallini R, Ricci-Vitiani L, Montano N, Mollinari C, Biffoni M, Cenci T, Pierconti F, Martini M, Maria RD, Larocca LM (2011) Expression of the stem cell marker CD133 in recurrent glioblastoma and its value for prognosis. Cancer 117:162–174PubMedCrossRef Pallini R, Ricci-Vitiani L, Montano N, Mollinari C, Biffoni M, Cenci T, Pierconti F, Martini M, Maria RD, Larocca LM (2011) Expression of the stem cell marker CD133 in recurrent glioblastoma and its value for prognosis. Cancer 117:162–174PubMedCrossRef
17.
go back to reference He J, Shan Z, Li L, Liu F, Liu Z, Song M, Zhu H (2011) Expression of glioma stem cell marker CD133 and O6-methylguanine-DNA methyltransferase is associated with resistance to radiotherapy in gliomas. Oncol Reports 26:1305–1313 He J, Shan Z, Li L, Liu F, Liu Z, Song M, Zhu H (2011) Expression of glioma stem cell marker CD133 and O6-methylguanine-DNA methyltransferase is associated with resistance to radiotherapy in gliomas. Oncol Reports 26:1305–1313
18.
go back to reference Liu G, Yuan X, Zeng Z, Tunici P, Ng H, Abdulkadir IR, Lu L, Irvin D, Black KL, Yu JS (2006) Analysis of gene expression and chemoresistance of CD133+ cancer stem cells in glioblastoma. Mol Cancer 5:67–78PubMedCrossRef Liu G, Yuan X, Zeng Z, Tunici P, Ng H, Abdulkadir IR, Lu L, Irvin D, Black KL, Yu JS (2006) Analysis of gene expression and chemoresistance of CD133+ cancer stem cells in glioblastoma. Mol Cancer 5:67–78PubMedCrossRef
19.
go back to reference Hermansen SK, Christensen KG, Jensen SS, Kristensen BW (2011) Inconsistent immunohistochemical expression patterns of four different CD133 antibody clones in glioblastoma. J Histochem Cytochem 59:391–407PubMedCrossRef Hermansen SK, Christensen KG, Jensen SS, Kristensen BW (2011) Inconsistent immunohistochemical expression patterns of four different CD133 antibody clones in glioblastoma. J Histochem Cytochem 59:391–407PubMedCrossRef
20.
go back to reference Metellus P, Nanni-Metellus I, Delfino C, Colin C, Tchogandjian A, Coulibaly B, Fina F, Loundou A, Barrie M, Chinot O, Ouafik L, Figarella-Branger D (2011) Prognostic impact of CD133 mRNA expression in 48 glioblastoma patients treated with concomitant radiotherapy: a prospective patient cohort at a single institution. Ann Surg Oncol 18:2937–2945PubMedCrossRef Metellus P, Nanni-Metellus I, Delfino C, Colin C, Tchogandjian A, Coulibaly B, Fina F, Loundou A, Barrie M, Chinot O, Ouafik L, Figarella-Branger D (2011) Prognostic impact of CD133 mRNA expression in 48 glioblastoma patients treated with concomitant radiotherapy: a prospective patient cohort at a single institution. Ann Surg Oncol 18:2937–2945PubMedCrossRef
21.
go back to reference Yan H, Parsons W, Jin G, McLendon R, Rasheed A, Yuan W, Kos I, Batinic-Haberle I, Jones S, Riggins GJ, Friedman H, Friedman A, Reardon D, Herndon J, Kinzler KW, Velculescu VE, Vogelstein B, Bigner DD (2009) IDH1 and IDH2 mutations in gliomas. N Engl J Med 360:765–773PubMedCrossRef Yan H, Parsons W, Jin G, McLendon R, Rasheed A, Yuan W, Kos I, Batinic-Haberle I, Jones S, Riggins GJ, Friedman H, Friedman A, Reardon D, Herndon J, Kinzler KW, Velculescu VE, Vogelstein B, Bigner DD (2009) IDH1 and IDH2 mutations in gliomas. N Engl J Med 360:765–773PubMedCrossRef
22.
go back to reference Rakheja D, Konoplev S, Medeiros LJ, Chen W (2012) IDH mutations in acute myeloid leukemia. Hum Pathol 43:1541–1551 Rakheja D, Konoplev S, Medeiros LJ, Chen W (2012) IDH mutations in acute myeloid leukemia. Hum Pathol 43:1541–1551
23.
go back to reference Lee D, Suh YL, Kang SY, Park TI, Jeong JY, Kim SH (2013) IDH1 mutations in oligodendroglial tumors: comparative analysis of direct sequencing, pyrosequencing, immunohistochemistry, Nested PCR and PNA-mediated clamping PCR. Brain Pathol 23:285–293PubMedCrossRef Lee D, Suh YL, Kang SY, Park TI, Jeong JY, Kim SH (2013) IDH1 mutations in oligodendroglial tumors: comparative analysis of direct sequencing, pyrosequencing, immunohistochemistry, Nested PCR and PNA-mediated clamping PCR. Brain Pathol 23:285–293PubMedCrossRef
24.
go back to reference Kim HJ, Lee KY, Kim YC, Kim KS, Lee SY, Jang TW, Lee MK, Shin KC, Lee GH, Lee JC, Lee JE, Kim SY (2012) Detection and comparison of peptide nucleic acid-mediated real-time polymerase chain reaction clamping and direct gene sequencing for epidermal growth factor receptor mutations in patients with non-small cell lung cancer. Lung Cancer 75:321–325PubMedCrossRef Kim HJ, Lee KY, Kim YC, Kim KS, Lee SY, Jang TW, Lee MK, Shin KC, Lee GH, Lee JC, Lee JE, Kim SY (2012) Detection and comparison of peptide nucleic acid-mediated real-time polymerase chain reaction clamping and direct gene sequencing for epidermal growth factor receptor mutations in patients with non-small cell lung cancer. Lung Cancer 75:321–325PubMedCrossRef
25.
go back to reference Oh JE, Lim HS, An CH, Jeong EG, Han JY, Lee SH, Yoo NJ (2010) Detection of low-level KRAS mutations using PNA-mediated asymmetric PCR clamping and melting curve analysis with unlabeled probes. J Mol Diagn 12:418–424PubMedCrossRef Oh JE, Lim HS, An CH, Jeong EG, Han JY, Lee SH, Yoo NJ (2010) Detection of low-level KRAS mutations using PNA-mediated asymmetric PCR clamping and melting curve analysis with unlabeled probes. J Mol Diagn 12:418–424PubMedCrossRef
26.
go back to reference Metellus P, Colin C, Taieb D, Guedj E, Nanni-Metellus I, Paula AM, Colavolpe C, Fuentes S, Dufour H, Barrie M, Chinot O, Ouafik L, Figarella-Branger D (2011) IDH mutation status impact on in vivo hypoxia biomarkers expression: new insights from a clinical, nuclear imaging and immunohistochemical study in 33 glioma patients. J Neurooncol 105:591–600PubMedCrossRef Metellus P, Colin C, Taieb D, Guedj E, Nanni-Metellus I, Paula AM, Colavolpe C, Fuentes S, Dufour H, Barrie M, Chinot O, Ouafik L, Figarella-Branger D (2011) IDH mutation status impact on in vivo hypoxia biomarkers expression: new insights from a clinical, nuclear imaging and immunohistochemical study in 33 glioma patients. J Neurooncol 105:591–600PubMedCrossRef
27.
go back to reference Rodriguez FJ, Orr BA, Ligon KL, Eberhart CG (2012) Neoplastic cells are a rare component in human glioblastoma microvasculature. Oncotarget 3:98–106PubMed Rodriguez FJ, Orr BA, Ligon KL, Eberhart CG (2012) Neoplastic cells are a rare component in human glioblastoma microvasculature. Oncotarget 3:98–106PubMed
Metadata
Title
Correlation between the prognostic value and the expression of the stem cell marker CD133 and isocitrate dehydrogenase1 in glioblastomas
Authors
Jung Ha Shin
Youn Soo Lee
Yong-Kil Hong
Chang Suk Kang
Publication date
01-12-2013
Publisher
Springer US
Published in
Journal of Neuro-Oncology / Issue 3/2013
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI
https://doi.org/10.1007/s11060-013-1234-z

Other articles of this Issue 3/2013

Journal of Neuro-Oncology 3/2013 Go to the issue