Skip to main content
SpringerLink
Log in

Prognostic value of Ki-67 index in primary intracranial tumors of infants

  • Original Article
  • Published:
Child's Nervous System Aims and scope Submit manuscript

Abstract

Objective

Primary intracranial tumors are rare tumors in infants. They differ from those found in other pediatric age groups in terms of clinical presentation, histopathological diagnosis, adjuvant therapies, and outcome. Ki-67 index has also shown promising results as a prognostic factor in different types of intracranial tumors in children and adults. However, the importance and the best cutoff point of Ki-67 index in primary intracranial tumors of infants remains unclear. We aimed to analyze prognostic value of Ki-67 index in primary intracranial tumors of infants.

Methods

This study retrospectively reviewed the records of 28 infants undergoing surgical resection for primary intracranial tumors between April 2016 and March 2021. We analyzed clinical characteristics, tumor location, extent of resection, histopathological diagnosis, Ki-67 index, and overall survival (OS). To define the most relevant cutoff value for Ki-67 index, “Cutoff Finder” was used.

Results

The median age at diagnosis was 188 days for all patients. Fifteen of the patients were boys and 13 were girls. Tumors were located supratentorial in 13 patients and infratentorial in 15 patients. Gross total resection was performed in 7 of 13 supratentorial tumors and 9 of 15 infratentorial tumors. The mean Ki-67 index of the supratentorial tumors was 49.6%, the median was 55%; for infratentorial tumors, the mean was 49.9%, and the median was 70%. Tumor grade (p = 0.019) and Ki-67 index (p = 0.003) were found as significant predictors of OS in log-rank testing for Kaplan–Meier survival analysis. Univariate cox regression analysis identified high Ki-67 index as prognostic factor for worse OS, with hazard ratio of 8.852 (95% CI 1.95–64.80; p = 0.0108). High Ki-67 index was found as independent prognostic factor for worse OS in multivariate cox regression analysis (HR 7.036; 95% CI 1.229–65.82; p = 0.0457).

Conclusion

High-grade and high Ki-67 index were associated with worse outcome. Ki-67 index did show a distinct prognostic value for OS within our cohort at a cutoff value of 72.5%.

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

Similar content being viewed by others

Data Availability

Data is available and provided in Table 1.

References

  1. Buetow PC, Smirniotopoulos JG, Done S (1990) Congenital brain tumors: a review of 45 cases. AJNR Am J Neuroradiol 11:793–799

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Isaacs H (2002) I. Perinatal brain tumors: a review of 250 cases. Pediatr Neurol 27:249–261. https://doi.org/10.1016/s0887-8994(02)00472-1

    Article  PubMed  Google Scholar 

  3. Isaacs H (2002) II. Perinatal brain tumors: a review of 250 cases. Pediatr Neurol 27:333–342. https://doi.org/10.1016/s0887-8994(02)00459-9

    Article  PubMed  Google Scholar 

  4. Ozbek MA, Yardibi F, Genç B et al (2022) Pediatric brain tumors: a bibliometric analysis. Childs Nerv Syst 38:1095–1104. https://doi.org/10.1007/s00381-022-05506-7

    Article  PubMed  Google Scholar 

  5. Bishop AJ, McDonald MW, Chang AL, Esiashvili N (2012) Infant brain tumors: incidence, survival, and the role of radiation based on Surveillance, Epidemiology, and End Results (SEER) Data. Int J Radiat Oncol Biol Phys 82:341–347. https://doi.org/10.1016/j.ijrobp.2010.08.020

    Article  PubMed  Google Scholar 

  6. Al-Hussaini M, Swaidan M, Al-Jumaily U, Musharbash A (2013) Central nervous system tumors in the first year of life: a clinical and pathologic experience from a single cancer center. Childs Nerv Syst 29:1883–1891. https://doi.org/10.1007/s00381-013-2081-0

    Article  PubMed  Google Scholar 

  7. Jaing T-H, Wu C-T, Chen S-H et al (2011) Intracranial tumors in infants: a single institution experience of 22 patients. Childs Nerv Syst 27:415–419. https://doi.org/10.1007/s00381-010-1298-4

    Article  PubMed  Google Scholar 

  8. Mohanty CB, Shukla DP, Devi BI (2013) Brain tumors of infancy–an institutional experience and review of the literature. Pediatr Neurosurg 49:145–154. https://doi.org/10.1159/000358308

    Article  PubMed  Google Scholar 

  9. Jurkiewicz E, Brożyna A, Grajkowska W et al (2012) Congenital brain tumors in a series of 56 patients. Childs Nerv Syst 28:1193–1201. https://doi.org/10.1007/s00381-012-1798-5

    Article  PubMed  Google Scholar 

  10. Lasky JL, Choi EJ, Johnston S et al (2008) Congenital brain tumors: case series and review of the literature. J Pediatr Hematol Oncol 30:326–331. https://doi.org/10.1097/MPH.0b013e3181647bf0

    Article  PubMed  Google Scholar 

  11. Mehrotra N, Shamji MF, Vassilyadi M, Ventureyra ECG (2009) Intracranial tumors in first year of life: the CHEO experience. Childs Nerv Syst 25:1563–1569. https://doi.org/10.1007/s00381-009-0936-1

    Article  PubMed  Google Scholar 

  12. Shamji MF, Vassilyadi M, Lam CH et al (2009) Congenital tumors of the central nervous system: the MCH experience. Pediatr Neurosurg 45:368–374. https://doi.org/10.1159/000257526

    Article  PubMed  Google Scholar 

  13. Gopalakrishna KN, Chakrabarti D, Sadashiva N et al (2019) Perioperative factors affecting neurologic outcome in infants undergoing surgery for intracranial lesion: a retrospective study. World Neurosurg 130:e702–e708. https://doi.org/10.1016/j.wneu.2019.06.196

    Article  PubMed  Google Scholar 

  14. Henker C, Kriesen T, Schneider B et al (2019) Correlation of Ki-67 index with volumetric segmentation and its value as a prognostic marker in glioblastoma. World Neurosurg 125:e1093–e1103. https://doi.org/10.1016/j.wneu.2019.02.006

    Article  PubMed  Google Scholar 

  15. Andre F, Arnedos M, Goubar A et al (2015) Ki67–no evidence for its use in node-positive breast cancer. Nat Rev Clin Oncol 12:296–301. https://doi.org/10.1038/nrclinonc.2015.46

    Article  PubMed  Google Scholar 

  16. Zhao F, Zhang J, Li P et al (2018) Prognostic value of Ki-67 index in adult medulloblastoma after accounting for molecular subgroup: a retrospective clinical and molecular analysis. J Neurooncol 139:333–340. https://doi.org/10.1007/s11060-018-2865-x

    Article  CAS  PubMed  Google Scholar 

  17. Armocida D, Frati A, Salvati M et al (2020) Is Ki-67 index overexpression in IDH wild type glioblastoma a predictor of shorter progression free survival? A clinical and molecular analytic investigation. Clin Neurol Neurosurg 198:106126. https://doi.org/10.1016/j.clineuro.2020.106126

    Article  PubMed  Google Scholar 

  18. Moschovi M, Alexiou GA, Patereli A et al (2011) Prognostic significance of cyclin A and B1 in pediatric embryonal tumors. J Neurooncol 103:699–704. https://doi.org/10.1007/s11060-010-0451-y

    Article  CAS  PubMed  Google Scholar 

  19. Budczies J, Klauschen F, Sinn BV et al (2012) Cutoff Finder: a comprehensive and straightforward Web application enabling rapid biomarker cutoff optimization. PLoS ONE 7:e51862. https://doi.org/10.1371/journal.pone.0051862

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Zhu X, Chen L, Huang B et al (2020) The prognostic and predictive potential of Ki-67 in triple-negative breast cancer. Sci Rep 10:225. https://doi.org/10.1038/s41598-019-57094-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Takeuchi M, Kawakubo H, Mayanagi S et al (2019) Perioperative risk calculator for distal gastrectomy predicts overall survival in patients with gastric cancer. Gastric Cancer 22:624–631. https://doi.org/10.1007/s10120-018-0896-9

    Article  PubMed  Google Scholar 

  22. Camacho-Urkaray E, Santos-Juanes J, Gutiérrez-Corres FB et al (2018) Establishing cut-off points with clinical relevance for bcl-2, cyclin D1, p16, p21, p27, p53, Sox11 and WT1 expression in glioblastoma - a short report. Cell Oncol (Dordr) 41:213–221. https://doi.org/10.1007/s13402-017-0362-4

    Article  CAS  PubMed  Google Scholar 

  23. Zhai L, Bell A, Ladomersky E et al (2021) Tumor Cell IDO Enhances immune suppression and decreases survival independent of tryptophan metabolism in glioblastoma. Clin Cancer Res 27:6514–6528. https://doi.org/10.1158/1078-0432.CCR-21-1392

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Viaene AN, Pu C, Perry A et al (2021) Congenital tumors of the central nervous system: an institutional review of 64 cases with emphasis on tumors with unique histologic and molecular characteristics. Brain Pathol 31:45–60. https://doi.org/10.1111/bpa.12885

    Article  PubMed  Google Scholar 

  25. Hart M, Anderson-Mellies A, Beltrami A et al (2022) Population-based analysis of CNS tumor diagnoses, treatment, and survival in congenital and infant age groups. J Neurooncol 157:333–344. https://doi.org/10.1007/s11060-022-03967-z

    Article  PubMed  Google Scholar 

  26. Di Rocco C, Iannelli A, Ceddia A (1991) Intracranial tumors of the first year of life. A cooperative survey of the 1986–1987 Education Committee of the ISPN. Childs Nerv Syst 7:150–153. https://doi.org/10.1007/BF00776711

    Article  PubMed  Google Scholar 

  27. Cavalheiro S, Moron AF, Hisaba W et al (2003) Fetal brain tumors. Childs Nerv Syst 19:529–536. https://doi.org/10.1007/s00381-003-0770-9

    Article  PubMed  Google Scholar 

  28. Rai S (2009) Primitive neuroectodermal tumor (MB) versus atypical teratoid/rhabdoid tumors, an imaging dilemma! J Pediatr Neurosci 4:48–49. https://doi.org/10.4103/1817-1745.49111

    Article  PubMed  PubMed Central  Google Scholar 

  29. Oi S, Matsumoto S, Choi JU et al (1990) Brain tumors diagnosed in the first year of life in five Far-Eastern countries. Statistical analysis of 307 cases. Childs Nerv Syst 6:79–85. https://doi.org/10.1007/BF00307926

    Article  CAS  PubMed  Google Scholar 

  30. El-Gaidi MA, Eissa EM (2010) Infantile intracranial neoplasms: characteristics and surgical outcomes of a contemporary series of 21 cases in an Egyptian referral center. Pediatr Neurosurg 46:272–282. https://doi.org/10.1159/000321540

    Article  PubMed  Google Scholar 

  31. Murshid WR, Siquiera E, Rahm B, Kanaan I (1994) Brain tumors in the first 2 years of life in Saudi Arabia. Childs Nerv Syst 10:430–432. https://doi.org/10.1007/BF00303607

    Article  CAS  PubMed  Google Scholar 

  32. Serowka K, Chiu Y, Gonzalez I et al (2010) Central nervous system (CNS) tumors in the first six months of life: the Children’s Hospital Los Angeles experience, 1979–2005. Pediatr Hematol Oncol 27:90–102. https://doi.org/10.3109/08880010903447342

    Article  CAS  PubMed  Google Scholar 

  33. Toescu SM, James G, Phipps K et al (2019) Intracranial neoplasms in the first year of life: results of a third cohort of patients from a single institution. Neurosurgery 84:636–646. https://doi.org/10.1093/neuros/nyy081

    Article  PubMed  Google Scholar 

  34. Rivera-Luna R, Medina-Sanson A, Leal-Leal C et al (2003) Brain tumors in children under 1 year of age: emphasis on the relationship of prognostic factors. Childs Nerv Syst 19:311–314. https://doi.org/10.1007/s00381-003-0738-9

    Article  PubMed  Google Scholar 

  35. Mapstone TB, Warf BC (1991) Intracranial tumor in infants: characteristics, management, and outcome of a contemporary series. Neurosurgery 28:343–348

    Article  CAS  PubMed  Google Scholar 

  36. Qaddoumi I, Sultan I, Gajjar A (2009) Outcome and prognostic features in pediatric gliomas: a review of 6212 cases from the Surveillance, Epidemiology, and End Results database. Cancer 115:5761–5770. https://doi.org/10.1002/cncr.24663

    Article  PubMed  Google Scholar 

  37. Brown K, Mapstone TB, Oakes WJ (1997) A modern analysis of intracranial tumors of infancy. Pediatr Neurosurg 26:25–32. https://doi.org/10.1159/000121157

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Istanbul Medipol University, School of Medicine, Department of Neurosurgery, TEM Goztepe exit, Bagcila, Istanbul, Turkey

    Alican Tahta & Nejat Akalan

Authors
  1. Alican Tahta
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nejat Akalan
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Alican Tahta collected data, contributed to statistical analysis, prepared, and wrote the main manuscript. Nejat Akalan supervised and revised the manuscript.

Corresponding author

Correspondence to Alican Tahta.

Ethics declarations

Ethics approval and consent to participate

This study was approved by Institutional Ethics Committee of Istanbul Medipol University (Ethics approval number: 949). Informed consent was obtained from the parents or legal representatives.

Consent for publication

All authors approved the final version of the manuscript.

Conflict of interest

The authors declare that they have no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tahta, A., Akalan, N. Prognostic value of Ki-67 index in primary intracranial tumors of infants. Childs Nerv Syst 39, 369–377 (2023). https://doi.org/10.1007/s00381-022-05822-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00381-022-05822-y

Keywords

Search

Navigation