Clinico-pathological and molecular characterization of diffuse midline gliomas: is there a prognostic significance?

• Published in: Neurological sciences Vol. 42; no. 3; pp. 925 - 934
• Main Authors: Manjunath, Niveditha, Jha, Prerana, Singh, Jyotsna, Raheja, Amol, Kaur, Kavneet, Suri, Ashish, Garg, Ajay, Sharma, Mehar Chand, Sarkar, Chitra, Mohan, Madan, Mani, Kalaivani, Suri, Vaishali
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01-03-2021; Springer Nature B.V
• Subjects: Adult; Brain Neoplasms - genetics; Brain stem; Child; Demography; Glioma; Glioma - genetics; Histones - genetics; Humans; Immunohistochemistry; Isocitrate Dehydrogenase - genetics; Medical prognosis; Medicine; Medicine & Public Health; Mutants; Mutation; Neurology; Neuroradiology; Neurosciences; Neurosurgery; Original Article; Pediatrics; Prognosis; Psychiatry; Survival; Survival analysis; Thalamus; Survival analysis; Adults; Diffuse midline gliomas; H3K27M mutation; Overall survival; Pediatric
• ISSN: 1590-1874; 1590-3478
• DOI: 10.1007/s10072-020-04489-0

Purpose
H3K27M mutant diffuse midline gliomas (DMGs) are considered grade IV irrespective of histological features and have dismal prognosis. We evaluated clinico-pathologic, radiological, and molecular characteristics of DMGs across all ages.
Methods
One twenty-six DMGs were identified over 10 years. Immunohistochemistry was done for H3K27M, ATRX, IDH1, and p53, and Sanger sequencing performed for IDH1 and H3K27M mutation. Patient demographics and clinico-radiologic characteristics were reviewed and survival analysis performed.
Results
DMGs comprised 5.3% of all gliomas with 49.2% H3K27M mutant and 50.8% wild types. Majority (75.68%) of pediatric and 38.20% of adults were H3K27M mutant (
p
 = 0.0001). Amongst H3K27M mutants, brainstem (46.43%) was the commonest location in pediatric and thalamus (61.76%) in adults. H3K27M mutation was mutually exclusive with IDH mutation in 93.55%, while p53, ATRX mutation were seen in 56.4% and 30.6% cases respectively. Software-based immunohistochemistry evaluation (H-scoring) showed 99.2% concordance with sequencing for H3K27M mutation. Radiologically, no significant difference in contrast enhancement was seen between mutant and wild types (
p
 = 0.05). The difference in overall survival (OS) was not significant in mutant versus wild types, with age or location. Tumor resection independently and on correlation with H3K27M did not influence OS (
p
 = 0.51 and
p
 = 0.47). Adjuvant therapy impacted survival significantly in adults (
p
 = 0.0009), however, not in pediatric cases (
p
 = 0.06).
Conclusions
The study highlights the differences in frequency and location of pediatric and adult DMGs. IHC (H-scoring) for H3K27M mutation is an excellent surrogate for sequencing. Prognosis remains dismal irrespective of age, location, and H3K27M status. Potential therapeutic targets need to be explored.