Skip to main content
SpringerLink
Log in

Expression of oligodendroglial differentiation markers in pilocytic astrocytomas identifies two clinical subsets and shows a significant correlation with proliferation index and progression free survival

  • clinical-patient studies
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

The growth pattern of pilocytic astrocytoma (PAs) is unpredictable. Gene expression profiling has recently demonstrated an inverse relationship between myelin basic protein (MBP) expression and progression free survival (PFS) in PAs. We present here the pattern of expression of oligodendroglial differentiation markers (ODMs) in PAs by immunohistochemistry and their correlation with PI and PFS. Sixty-four cases of PA were reviewed and representative sections were stained for Ki-67 and ODMs, including MBP, platelet-derived growth factor receptor-α (PDGFR-α), Olig-1, and Olig-2. Sections were graded semi-quantitatively for intensity (I: 0–3+) and extent (E: 0–4+) of staining. PI was expressed as a percentage of Ki-67 positive cells. Immunoreactivity of MBP, PDGFR-α, Olig-1, and Olig-2 was observed in 84, 56, 97, and 75% of cases, respectively. There was a statistically significant inverse correlation between MBP expression and PI (r 2 = .696, p  = .014). A positive correlation was observed between PDGFR-α and PI (r 2 = .727, p  = .011). Further analysis showed a significant difference in PFS between low expressors [I + E score ≤ 3] and high expressors (I + E score ≥ 4) for PDGFR-α with p  < .001. Notably, there was a significant difference in PFS between high expressors of MBP and high expressors of PDGFR-α with p  < .001. These results suggest that expression of ODMs, especially MBP and PDGFR-α, may identify two clinical subsets of PA. In addition, we have shown the expression of 4 different ODMs in PAs, which may support the possibility that PAs arise from oligodendrocyte progenitor/precursor cells probably similar to the O2A progenitor cells in the mouse.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Abbreviations

CNS:

Central nervous system

E:

Extent

I:

Intensity

IHC:

Immunohistochemistry

LI:

Labeling index

MBP:

Myelin basic protein

ODM:

Oligodendroglial differentiation marker

PA:

Pilocytic astrocytoma

PDGFR:

Platelet-derived growth factor receptor

PFS:

Progression free survival

PI:

Proliferation index

WHO:

World Health Organization

References

  1. Burger PC, Scheithauer BW, Paulus W, Szymas J, Giannini C, Kleihues P (2000) Pilocytic astrocytoma. In: Kleihues P, Cavenee WK (ed) World Health Organization classification of tumours. Pathology and genetics of tumours of the nervous system. IARC Press, Lyon, pp 45–51

    Google Scholar 

  2. Central Brain Tumor Registry of the United States (CBTRUS). http://www.cbtrus.org/2005–2006/2005–2006.html. Cited 16 March 2007

  3. Gajjar A, Sanford RA, Heideman R, Jenkins JJ, Walter A, Li Y, Langston JW, Muhlbauer M, Boyett JM, Kun LE (1997) Low grade astrocytoma: a decade of experience at St. Jude Children’s Research Hospital. J Clin Oncol 15:2792–2799

    PubMed  CAS  Google Scholar 

  4. Wong KK, Chang YM, Tsang YT, Perlaky L, Su J, Adesina A, Armstrong DL, Bhattacharjee M, Dauser R, Blaney SM, Chintagumpala M, Lau CC (2005) Expression analysis of juvenile pilocytic astrocytomas by oligonucleotide microarray reveals two potential subgroups. Cancer Res 65:76–84

    PubMed  CAS  Google Scholar 

  5. Bowers DC, Gargan L, Kapur P, Reisch JS, Mulne AF, Shapiro KN, Elterman RD, Winick NJ, Margraf LR (2003) Study of the MIB-1 labeling index as a predictor of tumor progression in pilocytic astrocytomas in children and adolescents. J Clin Oncol 21:2968–2973

    Article  PubMed  Google Scholar 

  6. Roessler K, Bertalanffy A, Jezan H, Ba-Ssalamah A, Slavc I, Czech T, Budka H (2002) Proliferative activity as measured by MIB-1 labeling index and long-term outcome of cerebellar juvenile pilocytic astrocytomas. J Neuro-Oncol 58:141–146

    Article  Google Scholar 

  7. Haapasalo H, Sallinen S-L, Sallinen P, Helen P, Jaaskelainen J, Salmi TT, Paetau A, Paljarvi L, Visakorpi T, Kalimo H (1999) Clinicopathological correlation of cell proliferation, apoptosis and p53 in cerebellar pilocytic astrocytomas. Neuropathol Appl Neurobiol 25:134–142

    Article  PubMed  CAS  Google Scholar 

  8. Machen SK, Prayson RA (1998) Cyclin D1 and MIB-1 immunohistochemistry in pilocytic astrocytomas: a study of 48 cases. Hum Pathol 29:1511–1516

    Article  PubMed  CAS  Google Scholar 

  9. Palma L, Celli P, Mariottini A (2004) Long-term follow-up of childhood cerebellar astrocytomas after incomplete resection with particular reference to arrested growth or spontaneous tumour regression. Acta Neurochir (Wien) 146:581–588

    Article  CAS  Google Scholar 

  10. Dirven CM, Koudstaal J, Mooij JJ, Molenaar WM (1998) The proliferative potential of the pilocytic astrocytoma: the relation between MIB-1 labeling and clinical and neuro-radiological follow-up. J Neurooncol 37:9–16

    Article  PubMed  CAS  Google Scholar 

  11. Distelmaier F, Janssen G, Mayatepek E, Schaper J, Gobel U, Rosenbaum T (2006) Disseminated pilocytic astrocytoma involving brain stem and diencephalons: a history of atypical eating disorder and diagnostic delay. J Neurooncol 79:197–201

    Article  PubMed  Google Scholar 

  12. Aryan HE, Meltzer HS, Lu DC, Ozgur BM, Levy ML, Bruce DA (2005) Management of pilocytic astrocytoma with diffuse leptomeningeal spread: two cases and review of the literature. Childs Nerv Syst 21:477–481

    Article  PubMed  Google Scholar 

  13. Komotar RJ, Burger PC, Carson BS, Brem H, Olivi A, Goldthwaite PT, Tihan T (2004) Pilocytic and pilomyxoid hypothalamic/chiasmatic astrocytomas. Neurosurgery 54:72–80

    Article  PubMed  Google Scholar 

  14. Fernandez C, Figarella-Branger D. Girard N, Bouvier-Labit C, Gouvernet J, Paz Paredes A, Lena G. (2003) Pilocytic astrocytomas in children: prognostic factors–a retrospective study of 80 cases. Neurosurgery 53:544–555

    Article  PubMed  Google Scholar 

  15. Shih AH, Holland EC (2006) Platelet-derived growth factor (PDGF) and glial tumorigenesis. Cancer Lett 232:139–147

    Article  PubMed  CAS  Google Scholar 

  16. Hart IK, Richardson WD, Bolsover SR, Raff MC (1989) PDGF and intracellular signaling in the timing of oligodendrocyte differentiation. J Cell Biol 109:3411–3417

    Article  PubMed  CAS  Google Scholar 

  17. Pringle N, Collarini EJ, Mosley MJ, Heldin CH, Westermark B, Richardson WD (1989) PDGF A chain homodimers drive proliferation of bipotential (O-2A) glial progenitor cells in the developing rat optic nerve. EMBO J 8:1049–1056

    PubMed  CAS  Google Scholar 

  18. Richardson WD, Pringle N, Mosley MJ, Westermark B, Dubois-Dalcq M (1988) A role for platelet-derived growth factor in normal gliogenesis in the central nervous system. Cell 53:309–319

    Article  PubMed  CAS  Google Scholar 

  19. Butt AM, Hornby MF, Ibrahim M, Kirvell S, Graham A, Berry M (1997) PDGF-alpha receptor and myelin basic protein mRNA are not coexpressed by oligodendrocytes in vivo: a double in situ hybridization study in the anterior medullary velum of the neonatal rat. Mol Cell Neurosci 8:311–322

    Article  PubMed  CAS  Google Scholar 

  20. Varela M, Ranuncolo SM, Morandi A, Lastiri J, De Kier Joffe EB, Puricelli LI, Pallotta MG. (2004) EGF-R and PDGF-R, but not bcl-2, overexpression predict overall survival in patients with low-grade astrocytomas. J Surg Oncol 86:34–40

    Article  PubMed  CAS  Google Scholar 

  21. Wegner M (2001) Expression of transcription factors during oligodendroglial development. Microsc Res Tech 52:746–752

    Article  PubMed  CAS  Google Scholar 

  22. Lu QR, Yuk D, Alberta JA, Zhu Z, Pawlitzky I, Chan J, McMahon AP, Stiles CD, Rowitch DH (2000) Sonic hedgehog-regulated oligodendrocytes lineage genes encoding bHLH proteins in the mammalian central nervous system. Neuron 25:317–329

    Article  PubMed  CAS  Google Scholar 

  23. Ohnishi A, Sawa H, Tsuda M, Sawamura Y, Itoh T, Iwasaki Y, Nagashima K (2003) Expression of the oligodendroglial lineage-associated markers Olig1 and Olig2 in different types of human gliomas. J Neuropathol Exp Neurol 62:1052–1059

    PubMed  CAS  Google Scholar 

  24. Shoshan Y, Nishiyama A, Chang A, Mork S, Barnett GH, Cowell JK, Trapp BD, Staugaitis SM (1999) Expression of oligodendrocyte progenitor cell antigens by gliomas: implications for the histogenesis of brain tumors. Proc Natl Acad Sci USA 96:10361–10366

    Article  PubMed  CAS  Google Scholar 

  25. Raff MC, Miller RH, Noble M (1983) A glial progenitor cell that develops in vitro into an astrocyte or an oligodendrocyte depending on culture medium. Nature 303:390–396

    Article  PubMed  CAS  Google Scholar 

  26. Figarella-Branger D, Daniel L, Andre P, Guia S, Renaud W, Monti G, Vivier E, Rougon G (1999) The PEN5 epitope identifies an oligodendrocyte precursor cell population and pilocytic astrocytomas. Am J Pathol 155:1261–1269

    PubMed  CAS  Google Scholar 

  27. Sung CC, Collins R, Li J, Pearl DK, Coons SW, Scheithauer BW, Johnson PC, Yates AJ (1996) Glycolipids and myelin proteins in human oligodendrogliomas. Glycoconj J 13:433–443

    Article  PubMed  CAS  Google Scholar 

  28. Kamitani H, Masuzawa H, Sato J, Kanazawa I (1988) Mixed oligodendroglioma and astrocytoma: fine structural and immunohistochemical studies of four cases. J Neurol Sci 83:219–225

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgement

The authors thank Pediatric Brain Tumor Foundation (KKW) for their support.

Author information

Authors and Affiliations

  1. Department of Pathology, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA

    Hidehiro Takei, Vidya Mehta & Adekunle M. Adesina

  2. Department of Pathology, The Methodist Hospital, 6565 Fannin Street, Houston, TX, 77030, USA

    Hidehiro Takei

  3. Texas Children’s Cancer Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA

    Subashini T. Yogeswaren, Kwong-Kwok Wong, Murali Chintagumpala & Ching C. Lau

  4. Department of Neurosurgery, Baylor College of Medicine, Houston, TX, USA

    Robert C. Dauser

Authors
  1. Hidehiro Takei
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Subashini T. Yogeswaren
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kwong-Kwok Wong
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Vidya Mehta
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Murali Chintagumpala
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Robert C. Dauser
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ching C. Lau
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Adekunle M. Adesina
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hidehiro Takei.

Additional information

This paper was presented, in part, at the 12th International Symposium on Pediatric Neuro-Oncology 2006, Nara, Japan, June 6–9, 2006.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Takei, H., Yogeswaren, S.T., Wong, KK. et al. Expression of oligodendroglial differentiation markers in pilocytic astrocytomas identifies two clinical subsets and shows a significant correlation with proliferation index and progression free survival. J Neurooncol 86, 183–190 (2008). https://doi.org/10.1007/s11060-007-9455-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11060-007-9455-7

Keywords

Search

Navigation