ABSTRACT
PURPOSE: Pediatric high-grade gliomas (pHGGs) constitute almost 15% of all childhood brain tumors. Recurrent mutations such as H3K27M mutation in H3F3A and HIST1H3B genes encoding histone H3 and its variants were identified in approximately 30% of pediatric glioblastomas. This study aimed to ascertain the morphological and molecular characteristics of pHGGs with H3K27M mutation. METHODS: In total, 61 cases of pHGGs (anaplastic astrocytoma, 12; glioblastomas, 49) from four university hospitals were studied. The histomorphological features were examined and immunohistochemistry was performed to evaluate the mutation status of H3K27M, ATRX, IDH1, BRAF V600E, and p53 genes. RESULTS: The study comprised 25 females and 36 males (age range, 1-18 years) with a clinical follow-up of up to 108 months. From the total, 31 patients were positive for H3K27M mutation located in the midline, mostly in the pons and thalamus. H3K27M mutation was commonly associated with ATRX loss (32.3%) and p53 (74.2%) immunoreactivity with a co-expression rate of 25.8%. While IDH1 mutation was not detected in pHGGs with H3K27M mutation, BRAFV600E mutation was rarely observed. Among the various histomorphological features, increased number of mitosis, increased Ki-67 proliferation index, and palisading and geographical necrosis along with small cell patterns were significantly associated with the H3K27M wild-type tumors. Focal infarct-like necrosis and pilomyxoid morphology was significantly associated with these tumors. CONCLUSION: H3K27M mutation occurs exclusively in pHGGs arising from the midline and presents with varied histomorphological features ranging from low-grade pilomyxoid astrocytoma to highly pleomorphic glioblastoma along with ATRX loss and p53 mutations.
Subject(s)
Astrocytoma/genetics , Brain Neoplasms/genetics , Glioblastoma/genetics , Glioma/genetics , Histones/genetics , Adolescent , Astrocytoma/pathology , Brain Neoplasms/pathology , Child , Child, Preschool , Female , Follow-Up Studies , Genes, p53/genetics , Glioblastoma/pathology , Glioma/pathology , Humans , Infant , Male , Mutation , Necrosis , Retrospective Studies , Survival Analysis , X-linked Nuclear Protein/geneticsABSTRACT
Patterns of cardiovascular risk factors in populations are not static over time. We examined trends in body mass index (BMI), parental smoking and blood pressure over a 15-year period in Turkish children aged 15-17 years. Two cross-sectional studies were performed in secondary schools in Turkey in 1989-1990 and 2004-2005. Study participants were 673 children in 1989-1990 and 640 adolescents in 2004-2005. Main outcome measures were weight, height, BMI, presence and amount of parental smoking, systolic and diastolic blood pressure. Age and sex matched comparisons were performed to assess temporal trends in these measures. Children in 2004-2005 had increased weight, height, BMI and decreased systolic and diastolic blood pressure in all age groups compared with children in 1989-1990. According to the international criteria, 3.4% of children were obese and 15.8% were overweight in 2005, compared to 0.7% obese and 4.2% overweight in 1990 (P<0.001). However, a decrease was noted in blood pressure; 16% were classified as hypertensive in 1989-1990 versus 8% in 2004-2005 (P<0.001). The prevalence and amount of parental smoking also decreased over the last 15 years. We observed significant changes in BMI and blood pressure in Turkish children over the last 15 years. Temporal trends in these parameters may indicate a change in the pattern of cardiovascular disease in this population.
