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Child's Nervous System

, Volume 35, Issue 9, pp 1537–1545 | Cite as

H3K27M, IDH1, and ATRX expression in pediatric GBM and their clinical and prognostic significance

  • Alok Mohan Uppar
  • Harsha Sugur
  • A. R. Prabhuraj
  • M. Bhaskara Rao
  • B. Indira Devi
  • S. Sampath
  • A. ArivazhaganEmail author
  • Vani Santosh
Original Article

Abstract

Purpose

Pediatric glioblastoma (pGBM) tumors have been identified as an entity distinct and different from the adult variety of GBM not only with respect to pathogenesis, genetics, and molecular alterations but also in clinical outcomes and overall survival. This study aims to evaluate the immunohistochemical profile of molecular markers in pediatric GBM and correlate them with clinical features and prognosis.

Materials and methods

We retrospectively analyzed 29 pGBMs (age range 3 to 18 years), operated at our institute between 2009 and 2014, and evaluated their clinical and histopathological features along with the immunohistochemical expression of clinically relevant molecular markers: H3K27M, p53, ATRX, and IDH1 (R132H), and correlated their expression with clinical features. We further assessed the prognostic value of these markers in our cohort of patients.

Results

The median overall survival (OS) of the cohort was 6.00 ± 0.882 months. The mean overall survival was 7.571 ± 1.118 months which was lower than in most studies. Preoperative Karnofsky Performance Score (KPS), extent of surgical resection, and adjuvant radiotherapy were found to be the clinical factors strongly influencing median survival (p < 0.05). Loss of ATRX expression was predominantly noted in hemispheric tumors (84%), while p53 staining was maximum in thalamic tumors (8 out of 9 cases). H3K27M mutant protein expression was noted in 8/9 thalamic tumors and 5/7 tumors in the brain stem-cerebellar-peduncular region. Patients with tumors showing H3K27M immunopositivity had the worst prognosis with a mean OS of 5 months ± 0.832 months, as against patients with H3K27M-immunonegative tumors, which was 10.143 ± 1.866 months(p = 0.006). Other markers like p53, ATRX, and IDH1 did not influence the prognosis in this patient cohort. ATRX loss of expression was associated with a better OS, with a trend to significance, and such an association has not been reported earlier.

Conclusions

Ours is one among the few studies from India describing the clinical parameters and evaluating the key immunohistochemical markers in pGBM and deriving their prognostic significance. The study reiterates the poor prognostic significance of H3K27M immunopositivity.

Keywords

Glioblastoma Pediatric H3K27M ATRX IDH1 Immunohistochemistry 

Notes

Acknowledgments

We would like to acknowledge Mr. MR Chandrashekar and Mrs. Hemavathy U for technical assistance and Mr. Manjunath K for the preparation of the picture montages.

Compliance with ethical standards

The study has been approved by the Institute Ethics committee, NIMHANS, Bangalore.

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Alok Mohan Uppar
    • 1
  • Harsha Sugur
    • 2
  • A. R. Prabhuraj
    • 1
  • M. Bhaskara Rao
    • 1
  • B. Indira Devi
    • 1
  • S. Sampath
    • 1
  • A. Arivazhagan
    • 1
    Email author
  • Vani Santosh
    • 2
  1. 1.Department of NeurosurgeryNational Institute of Mental Health and NeurosciencesBangaloreIndia
  2. 2.Department of NeuropathologyNational Institute of Mental Health and NeurosciencesBangaloreIndia

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