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Evaluation of osteopontin as a potential biomarker for central nervous system embryonal tumors

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Abstract

Osteopontin (OPN) is a protein linked to tumor growth, progression and metastasis of cancers. However, its role in the progression of central nervous system (CNS) embryonal tumors such as atypical teratoid/rhabdoid tumor (AT/RT), medulloblastoma (MB) and primitive neuroepithelial tumors (PNET) remains elusive. In this study, we investigated the value of OPN staining in differential diagnosis of AT/RT from MB and PNET, and assessed the correlation between OPN expression and patients’ prognosis. This retrospective study was conducted on tissue sections obtained from children cases with CNS embryonal tumors treated in Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine from 2006 to 2012 by immunohistochemistry (IHC). 49 cases were collected (11 AT/RTs, 25 MBs, and 13 PNETs), with a median follow-up time of 28.9 months. OPN expression in AT/RT was significantly higher than MB and PNET with the positive rates of 100, 32, and 23 %, respectively (P < 0.01). The specificity and sensitivity of OPN staining in diagnosing AT/RT are 97.4 and 90.9 %, respectively, as judged by strong OPN IHC staining level (+++). Patients who had positive OPN staining have increased risks of poorer median overall survival (hazard risk 5.54, 95 % CI 1.87–16.38) and tumor progression (hazard risk 14.47, 95 % CI 4.47–46.85). OPN is a valuable biomarker to aid in the differential diagnosis between AT/RT and MB/PNET. Moreover, OPN is a potential novel prognostic marker for CNS embryonal tumors.

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References

  1. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK (2007) WHO classification of tumours of the central nervous system, 4th edn. IARC Press, Lyon

    Google Scholar 

  2. Bailey P, Cushing H (1925) Medulloblastoma cerebelli, a common type of midcerebellar glioma of childhood. Arch Neurol Psychiatry 14:192–224

    Article  Google Scholar 

  3. Adesina AM, Hunter J (2010) Medulloblastoma. In: Tihan T, Fuller CE, Poussaint TY (eds) Atlas of pediatric brain tumors, 1st edn. Springer, New York, p 75

    Chapter  Google Scholar 

  4. Pomeroy SL, Tamayo P, Gaasenbeek M et al (2002) Prediction of central nervous system embryonal tumour outcome based on gene expression. Nature 415:436–442

    Article  CAS  PubMed  Google Scholar 

  5. Gilbertson RJ, Ellison DW (2008) The origins of medulloblastoma subtypes. Annu Rev Pathol 3:341–365

    Article  CAS  PubMed  Google Scholar 

  6. Lefkowity IB, Rorke LB, Packer RJ et al (1987) Atypical teratoid tumor of infancy: definition of an entity. Ann Neurol 22:448–449

    Google Scholar 

  7. Helseth E, Due-Tonnessen B, Wesenberg F et al (1999) Posterior fossa medulloblastoma in children and young adults (0–19 years): survival and performance. Childs Nerv Syst 15:451–455

    Article  CAS  PubMed  Google Scholar 

  8. Geyer JR, Sposto R, Jennings M et al (2005) Multiagent chemotherapy and deferred radiotherapy in infants with malignant brain tumors: a report from the children’s cancer group. J Clin Oncol 23:7621–7631

    Article  PubMed  Google Scholar 

  9. Chintagumpala M, Hassall T, Palmer S et al (2009) A pilot study of risk-adapted radiotherapy and chemotherapy in patients with supratentorial PNET. Neuro Oncol 11:33–40

    Article  PubMed Central  PubMed  Google Scholar 

  10. Athale UH, Duckworth J, Odame I et al (2009) Childhood atypical teratoid rhabdoid tumor of the central nervous system: a meta-analysis of observational studies. J Pediatr Hematol Oncol 31:651–663

    Article  PubMed  Google Scholar 

  11. Parwani AV, Stelow EB, Pambuccian SE et al (2005) Atypical teratoid/rhabdoid tumor of the brain: cytopathologic characteristics and differential diagnosis. Cancer 105:65–70

    Article  PubMed  Google Scholar 

  12. Bishop JA, Ali SZ (2012) Pediatric atypical teratoid/rhabdoid tumors: differential diagnosis. In: Hayat MA (ed) Pediatric cancer, volume 2: teratoid/rhabdoid, brain tumors, and glioma, 2012th edn. Springer, Dordrecht, pp 53–56

    Chapter  Google Scholar 

  13. Biegel JA, Tan L, Zhang F et al (2002) Alterations of the hSNF5/INI1 gene in central nervous system atypical teratoid/rhabdoid tumors and renal and extrarenal rhabdoid tumors. Clin Cancer Res 8:3461–3467

    CAS  PubMed  Google Scholar 

  14. Biegel JA, Kalpana G, Kundsen ES et al (2002) The role of INI and the SWI/SNF complex in the development of rhabdoid tumors: meeting summary from the workshop on childhood atypical teratoid/rhabdoid tumors. Cancer Res 62:323–328

    CAS  PubMed  Google Scholar 

  15. Oldberg A, Franzén A, Heinegård D (1986) Cloning and sequence analysis of rat bone sialoprotein (osteopontin) cDNA reveals an Arg-Gly-Asp cell-binding sequence. Proc Natl Acad Sci USA 83:8819–8823

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Konno S, Kurokawa M, Uede T et al (2011) Role of osteopontin, a multifunctional protein, in allergy and asthma. Clin Exp Allergy 41:1360–1366

    Article  CAS  PubMed  Google Scholar 

  17. Chen G, Zhang X, Li R et al (2010) Role of osteopontin in synovial Th17 differentiation in rheumatoid arthritis. Arthritis Rheumatol 62:2900–2908

    Article  CAS  Google Scholar 

  18. Carecchio M, Comi C (2011) The role of osteopontin in neurodegenerative diseases. J Alzheimers Dis 25:179–185

    CAS  PubMed  Google Scholar 

  19. Ahmed M, Behera R, Chakraborty G et al (2011) Osteopontin: a potentially important therapeutic target in cancer. Expert Opin Ther Targets 15:1113–1126

    Article  CAS  PubMed  Google Scholar 

  20. Shevde LA, Das S, Clark DW et al (2010) Osteopontin: an effector and an effect of tumor metastasis. Curr Mol Med 10:71–81

    Article  CAS  PubMed  Google Scholar 

  21. Weber GF, Lett GS, Haubein NC (2010) Osteopontin is a marker for cancer aggressiveness and patient survival. Br J Cancer 103:861–869

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Kao CL, Chiou SH, Chen YJ et al (2005) Increased expression of osteopontin gene in atypical teratoid/rhabdoid tumor of the central nervous system. Mod Pathol 18:769–778

    Article  CAS  PubMed  Google Scholar 

  23. Kao CL, Chiou SH, Ho DMT et al (2005) Elevation of plasma and cerebrospinal fluid osteopontin levels in patients with atypical teratoid/rhabdoid tumor. Am J Clin Pathol 123:297–304

    Article  CAS  PubMed  Google Scholar 

  24. Bruggers CS, Bleyl SB, Pysher T et al (2011) Clinicopathologic comparison of familial versus sporadic atypical teratoid/rhabdoid tumors (AT/RT) of the central nervous system. Pediatr Blood Cancer 56:1026–1031

    Article  PubMed Central  PubMed  Google Scholar 

  25. Fromowitz FB, Viola MV, Chao S et al (1987) Ras p21 expression in the progression of breast cancer. Hum Pathol 18:1268–1275

    Article  CAS  PubMed  Google Scholar 

  26. Iwanaga Y, Ueno M, Ueki M et al (2008) The expression of osteopontin is increased in vessels with blood-brain barrier impairment. Neuropathol Appl Neurobiol 34:145–154

    Article  CAS  PubMed  Google Scholar 

  27. Selkirk SM, Morrow J, Barone TA et al (2008) Elevation of osteopontin levels in brain tumor cells reduces burden and promotes survival through the inhibition of cell dispersal. J Neurooncol 86:285–296

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Toy H, Yavas O, Eren O et al (2009) Correlation between osteopontin protein expression and histological grade of astrocytomas. Pathol Oncol Res 15:203–207

    Article  CAS  PubMed  Google Scholar 

  29. Matusan-Ilijas K, Behrem S, Jonjic N et al (2008) Osteopontin expression correlates with angiogenesis and survival in malignant astrocytoma. Pathol Oncol Res 14:293–298

    Article  PubMed  Google Scholar 

  30. Woehrer A, Slavic I, Waldhoer T et al (2010) Incidence of atypical teratoid/rhabdoid tumors in children: a population-based study by the austrian brain tumor registry, 1996–2006. Cancer 116:5725–5732

    Article  PubMed  Google Scholar 

  31. Hollmann TJ, Hornick JL (2011) INI1-deficient tumors: diagnostic features and molecular genetics. Am J Surg Pathol 35:e47–e63

    Article  PubMed  Google Scholar 

  32. Judkins AR, Burger PC, Hamilton RL et al (2005) INI1 protein expression distinguishes atypical teratoid/rhabdoid tumor from choroid plexus carcinoma. J Neuropathol Exp Neurol 64:391–397

    CAS  PubMed  Google Scholar 

  33. Hasselblatt M, Gesk S, Oyen F et al (2011) Nonsense mutation and inactivation of SMARCA4 (BRG1) in an atypical teratoid/rhabdoid tumor showing retained SMARCB1 (INI1) expression. Am J Surg Pathol 35:933–935

    Article  PubMed  Google Scholar 

  34. Ma HI, Kao CL, Lee YY et al (2010) Differential expression profiling between atypical teratoid/rhabdoid and medulloblastoma tumor in vitro and in vivo using microarray analysis. Childs Nerv Syst 26:293–303

    Article  PubMed  Google Scholar 

  35. Chakraborty G, Jain S, Kundu GC (2008) Osteopontin promotes vascular endothelial growth factor-dependent breast tumor growth and angiogenesis via autocrine and paracrine mechanisms. Cancer Res 68:152–161

    Article  CAS  PubMed  Google Scholar 

  36. Jan HJ, Lee CC, Shih YL et al (2010) Osteopontin regulates human glioma cell invasiveness and tumor growth in mice. Neuro Oncol 12:58–70

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  37. Arıkök AT, Onder E, Seçkin H et al (2013) Osteopontin expressions correlate with WHO grades and predict recurrence in meningiomas. Brain Tumor Pathol. doi:10.1007/s10014-013-0152-2

    PubMed  Google Scholar 

  38. Lin CK, Tsai WC, Lin YC, Hueng DY (2012) Osteopontin predicts the behaviour of atypical meningioma. Histopathology 60:320–325

    Article  PubMed  Google Scholar 

  39. Tsai WC, Lee HS, Lin CK et al (2012) The association of osteopontin and LMX1A expression with World Health Organization grade in meningiomas and gliomas. Histopathology 61:844–856

    Article  PubMed  Google Scholar 

  40. Barresi V, Caffo M, Ieni A et al (2011) Osteoblastic meningiomas: clinico-pathological and immunohistochemical features of an uncommon variant. J Neurooncol 105:225–232

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by grants from the Major State Basic Research Development Program of China (973 program) (No. 2010CB945203), National Natural Science Foundation of China (No. 81271382), Program of Shanghai Subject Chief Scientist (A type) (No. 09XD1403300), and China Scholarship Council. The authors acknowledge Prof. Lifeng Wang and Xiangru Wu for referring samples for pathological diagnosis and staining assessment. The authors also acknowledge Mr. Wenzhu Zhang and Mrs. Yujin Feng for technical assistance in section preparation. We also acknowledge Dr. Kenneth Wu, Ms. Cydnie Maitrejean, Miss Chew Shan Hwu and Miss Joelle Yang for language assistance.

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical standards

This study was in accordance with the Declaration of Helsinki and had been approved by the Ethics Committee of Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine. (Approval No. XHEC-D-2012-017, please see attached page for ethical certification).

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Correspondence to Masahide Takahashi or Jie Ma.

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Han, YP., Ma, CK., Wang, SQ. et al. Evaluation of osteopontin as a potential biomarker for central nervous system embryonal tumors. J Neurooncol 119, 343–351 (2014). https://doi.org/10.1007/s11060-014-1484-4

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  • DOI: https://doi.org/10.1007/s11060-014-1484-4

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