Pediatric glioblastomas: A histopathological and molecular genetic study

Abstract

Glioblastoma multiforme (GBM) occurs rarely in children. Relatively few studies have been performed on molecular properties of pediatric GBMs. Our objective in this study was to evaluate the genetic alterations in pediatric GBM (age < or = 18 years) with special reference to p53, p16, and p27 protein expression, alterations of the epidermal growth factor receptor (EGFR), and deletion of the phosphate and tensin homolog gene (PTEN). Thirty cases of childhood GBMs reported between January 2002 and June 2007 were selected, and slides stained with hematoxylin and eosin were reviewed. Immunohistochemical staining was performed for EGFR, p53, p16, and p27, and tumor proliferation was assessed by calculating the MIB-1 labeling index (LI). Fluorescence in situ hybridization analysis was performed to evaluate for EGFR amplification and PTEN deletion. Histopathological features and MIB-1 LI were similar to adult GBMs. p53 protein expression was observed in 63%. Although EGFR protein overexpression was noted in 23% of cases, corresponding amplification of the EGFR gene was rare (5.5%). Deletion of the PTEN gene was also equally rare (5.5%). One case showed polysomy (chromosomal gains) of chromosomes 7 and 10. Loss of p16 and p27 immunoexpression was observed in 68% and 54% of cases, respectively. In pediatric de novo/primary GBMs, deletion of PTEN and EGFR amplification are rare, while p53 alterations are more frequent compared to primary adult GBMs. Frequency of loss of p16 and p27 immunoexpression is similar to their adult counterparts. This suggests that pediatric malignant gliomas are distinctly different from adult GBMs, highlighting the need for identification of molecular targets that may be adopted for future novel therapeutic strategies.

Treatment of high-grade glioma in children

“…İnfant GBM, de novo gelişim gösteren ve tamamen farklı bir antitedir. [5,6] Pediatrik YDG oluşumu, erişkin sekonder GBM patogeneziyle benzerlik gösterir ve p53 mutasyonunun normalden fazla ekspresyonu (%65), PDGF-A ve PDGFR-α (%60) ekspresyonunun artışına neden olarak patogenezde başlatıcı role sahiptir. Ancak pediatrik YDG oluşumu, henüz eriş-kin patogenezi kadar netlik kazanmamıştır.…”

Glioblastoma multiforme: Molecular characterization and current treatment strategy (Review)

“…The overexpression of the EGFR protein is observed in 23-40% of patients, and p53 gene mutations are very frequent, occurring in approximately 33-63% of patients (22)(23)(24). The genes overexpressed in GBM usually produce extracellular proteins, thereby providing possible therapeutic targets.…”

Glioblastoma multiforme with very rapid growth and long-term survival in children

“…The extent of surgical resection coupled with postoperative radiotherapy and chemotherapy seem to prolong survival. Our neuropathology colleagues performed molecular analysis of a subgroup of these patients and concluded that in pediatric primary GBMs, deletion of PTEN, and EGFR amplification were rare, while p53 alterations were more frequent as compared with primary adult GBMs [2].…”