Evaluation Of Prognostic Factors Of Midline Gliomas With H3K27M Mutation

Objective: Summarize the clinicopathological characteristics of gliomas in the midline,Analysis the relationship between H3K27 M mutation with age,lesion location,histologic subtypes,then evaluated of prognostic factors of gliomas in the midline.Methods: Tissue samples were retrieved from the Guangdong Sanjiu Brain Hospital,All tumors were reviewed by two Neuropathologists and diagnosed according to the revised WHO 2016 classification of Tumors of the central Nervous System.Analyze neuroimaging features,histological type,Immunohistochemistry expression characteristics of H3K27 M,p53 and ATRX.Correlation between H3K27 M gene status with various factors were assessed using the Chi square test.The Kaplan meire or The Cox regression was used to analyzed the value of various clinical and histological prognostic factors.Results: 1.All 180 tumors with gliomas in the midline,range1-71 years(median age of 30 years).67 cases located brain stem(37.2%),63 cases located thalamus.H3K27 M mutation were found in 74 cases(41.1%)of the tumors.The presence of H3K27 M mutations was signifcantly related to patient age?18 years(P = 0.009),and occurred significantly Brain Stem(P=0.0003).2.All 74 cases occurred H3K27 M mutations was found in different histologic subtypes,in 59(32.2%)Diffuse astrocytomas,in 10(5.6%)Pilocytic astrocytomas.IDH1R132 H was wild-type in all tumors,p53 overexpression in 24/38(63.2%),ATRX expression deletion in 19/52(36.5%).Patients with H3K27 M mutation in Diffuse astrocytomas and Pilocytic astrocytomas were significantly(P=0.016).Without the mutation of IDH mutations(P=0.03),associated with p53 overexpression(P=0.013)and ATRX expression deletion(P<0.001).3.In our study,all cases of the median survival period was 13.6 months.Diffuse midline glioma with H3K27 M mutations median survival period was 11.8 months,and H3K27M-mutant was significantly with poor prognosis(P=0.011).The Median survival period was 14.5 months located in thalamus,prognosis without of H3K27 M mutation(P=0.46).The Median survival period was 12.2 months located in Brain stem,and associated with mutation of H3K27M(P=0.008).4.The outcome of adult Gliomas were good than Pediatric(?18 years)Gliomas(P=0.049),although they were also accompanied by H3K27M-mutant.H3K27 M mutation diffuse astrocytomas have a worse prognosis than circumscribed astrocytomas(P=0.036).Poor prognosis was distribution of H3K27 M mutation types among high-grade(WHO ?-?grade)was different low-grade(WHO?-?grade)were observed.There was no signifcantly association between WHO? grade with WHO? grade(P=0.46)or between WHO ? grade with WHO? grade(P=0.12).Conclusion: 1.The majority of H3K27 M mutations were observed of gliomas in midline,frequently encountered brain stem and thalamus,and occur at any age,more often in children or younger.Diffuse astrocytomas is the most common histologic,also be circumscribed gliomas,most common H3K27 M mutation Pilocytic astrocytomas which are occur midline.H3K27 M mutations correlation between p53 overexpression and ATRX expression deletion.2.H3K27 M could not be independent of location and histopathology of tumor to determine prognosis.H3K27 M mutation was associated with poor prognosis of brainstem glioma,but not with thalamic glioma.The prognosis of diffuse midline glioma with H3K27 M mutation is worse than circumscribed glioma with H3K27 M mutation,and circumscribed glioma with H3K27 M mutation is worse than that of H3K27 M wild type 3.H3K27 M could not be isolated from histological grade to determine the prognosis independently.For H3K27 M mutant midline glioma,histological classification still has prognostic stratification value.It is suggested to divide tumors into H3K27 M mutant low-grade glioma and H3K27 M mutant high-grade glioma,so as to better guide clinical diagnosis and treatment.