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Is H3K27me3 status really a strong prognostic indicator for pediatric posterior fossa ependymomas? A single surgeon, single center experience

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Abstract

Purpose

Posterior fossa ependymomas (PFE) are among the most frequently occurring solid tumors in children. Their definitive treatment is surgical excision and adjuvant radio-chemotherapy. This study aimed to investigate prognostic effects of age, H3K27me3 status, extent of resection, radiation treatment (RT), Ki67 index, WHO grade, and ATRX and H3K27M mutations in PFE patients.

Methods

This retrospective study included 42 pediatric patients with PFE who had undergone operation at our institution between 1996 and 2018. Patient demographics and treatment information were obtained from patient notes. Information on radiological location of tumors (median vs paramedian), extent of tumor resection, and recurrence was obtained from preoperative and postoperative magnetic resonance imaging. Formalin-fixed paraffin-embedded tumor samples were evaluated for H3K27me3 immunostaining, Ki67 index, WHO grades, and ATRX and H3K27M mutations. Tumor samples with global reduction in H3K27me3 were grouped as posterior fossa ependymoma group A (PFA) and those with H3K27me3 nuclear immunopositivity as posterior fossa ependymoma group B (PFB). We evaluated the cohort’s 5-year progression-free survival (PFS) and overall survival (OS).

Results

There were 20 (47.6%) female and 22 (52.4%) male patients in the cohort. The mean age of patients was 4.4 (range, 0.71–14.51) years. Overall, tumors in 31 (73.8%) and 11 (26.2%) patients were found to be PFA and PFB, respectively. There was no statistically significant age or sex difference between PFA and PFB. All patients received chemotherapy, whereas only 28 (66.6%) received RT. The WHO grades of PFA were statistically higher than those of PFB. There was no significant difference between PFA and PFB in terms of extent of resection, disease recurrence, and survival parameters. Nine of 42 tumor samples had ATRX mutations. One patient with PFA showed H3K27M mutation. Age, WHO grade, H3K27me3 status, and RT had no effect on patients’ PFS and OS. Patients with total surgical excisions had significantly better PFS and OS rates. Those with Ki67 < 50% also had better OS rates.

Conclusions

Determining H3K27me3 status by immunohistochemistry is a widely accepted method for molecular subgrouping of PFEs. Most of the reports in the literature state that molecular subgroups of PFEs have significantly different clinical outcomes. However, in our present series, we have shown that the extent of surgical excision is still the most important prognostic indicator in PFEs. We also conclude that the prognostic effect of H3K27me3 status–based molecular subgrouping may be minimized with a more aggressive surgical strategy followed in PFAs.

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Acknowledgments

We would like to thank Dr. Alp Inanıcı for his valuable cooperation during statistical data analysis of this study.

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Authors and Affiliations

  1. Department of Neurosurgery, Division of Pediatric Neurosurgery, Acıbadem University School of Medicine, Istanbul, Turkey

    Bahattin Tanrıkulu & M. Memet Özek

  2. Department of Pathology, Acıbadem University School of Medicine, Istanbul, Turkey

    Ayça Erşen Danyeli

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  1. Bahattin Tanrıkulu
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Correspondence to Bahattin Tanrıkulu.

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This retrospective study was approved by ethical committee of Acibadem University School of Medicine, Istanbul, Turkey. Informed consent was obtained from patients’ legal guardians.

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Informed consent was obtained from all individual participants included in the study.

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Tanrıkulu, B., Danyeli, A.E. & Özek, M.M. Is H3K27me3 status really a strong prognostic indicator for pediatric posterior fossa ependymomas? A single surgeon, single center experience. Childs Nerv Syst 36, 941–949 (2020). https://doi.org/10.1007/s00381-020-04518-5

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