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To investigate the expression and significance of H3K27M and Ki-67 in pediatric glioma. Methods: Immunohistochemistry was used to detect the expression of H3K27M and Ki-67 in 38 patients with pediatric glioma and 10 patients with normal brain tissue, who enrolled in Yuquan Hospital, Tsinghua University from November 2013 to June 2018. The results were analyzed using appropriate statistical methods. Results: The positive expression of H3K27M was not significantly correlated with gender, age, and tumor site (P>0.05). However, it was significantly correlated with the tumor pathological grade (P0.05). However, it was significantly correlated with the pathological grade and tumor site (P0.05). There were significant correlations between the tumor pathological grade, tumor location, H3K27M protein-positive, Ki-67 high label index, and patient survival time (P<0.05). Conclusions: The expression level of H3K27M and Ki-67 appeared to be related to the pathological grade and prognosis of pediatric glioma. Besides, the expression of H3K27M and Ki-67 protein in glioma tissue were correlated. This could be useful for studying the occurrence and development of glioma as well as investigating potential targeted therapy options.
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Objective: To investigate multimodal MRI features of diffuse midline glioma, H3 K27M mutant. Methods Multimodal MRI features, including plain and enhanced MRI, DWI and dynamic susceptibility contrast (DSC)-PWI of 10 patients with pathologically proved diffuse midline glioma, H3 K27M mutant were retrospectively analyzed. The location, size, edema, signal characteristics, diffusion, enhancement characteristics, etc. of the tumors were observed. Results Among 10 patients, 8 lesions located at thalamus, 1 at medulla and cervical cord, 1 at hypothalamus. The mean maximum tumor diameter was (5.56±0.42)cm, and the mean peritumoral edema distance was (1.33±0.34)cm. The tumors appeared as low signal intensity on T1WI and high signal intensity on T2WI, with small patchy short T1 and short T2 signal within lesions. Cystic lesions were observed in 3 lesions, and necrosis and hemorrhage were found in both 7 lesions. Nine lesions demonstrated marked enhancement, with ringlike pattern in 5 lesions, nodular pattern in 3 lesions and patchy pattern in 1 lesion. There was no enhancement in 1 lesion. Hydrocephalus were found in 9 patients. DWI showed restricted diffusion in 8 patients, with mean relative ADC of 1.26±0.12 and minimum relative ADC of 1.12±0.12. In 5 patients who underwent DSC-PWI, markedly high perfusion was demonstrated in 3 patients, moderate perfusion in 1 patient and low perfusion 1 patient demonstrated. The maximum relative cerebral blood volumewas 2.92±0.49. Conclusion: Multimodal MRI manifestations of diffuse midline glioma, H3 K27M mutant are various, but similar to those of high-grade gliomas. Molecular pathology may be considered for deferential diagnosis.
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Objective@#To investigate the role of H3K27M mutant in spinal cord glioma, specifically the correlation between H3K27M mutation and histological grade or prognosis.@*Methods@#Twenty-four cases of paraffin-embedded spinal cord glioma tissues and clinical data were collected from November 2014 to August 2016 at the Beijing Tsinghua Changgung Hospital. There were 13 males and 11 females, and the age ranged from 3 to 66 years. All the cases were reviewed histologically, and immunohistochemical H3K27M staining and H3 gene detection were performed. The correlation between H3 gene mutation and histological grading and prognosis of spinal cord gliomas were investigated and relevant literature reviewed.@*Results@#Eleven of 24 cases showed H3K27M gene mutation, and was concordant with the result of immunohistochemistry. Gliomas in the mutant group were all high-grade gliomas with mean patients′ age of (30.0±11.5) years, and a male to female ratio of 7:4. Thirteen cases were wild-type, and these included four high-grade gliomas, with mean patients′ age (31.3±22.4) years, and a male to female ratio of 6∶7. The tumors in the mutant group were mainly located in cervical 4-7 and thoracic 11-12 segments, respectively, and the incidence of tumors in the lower thoracic segments (thoracic 11-12) was higher than that in the wild type group. Outcome data were available for all patients. The median survival of mutant group was 19.5 months, but most patients in the wild-type group were alive at the end of the follow-up period.@*Conclusion@#Gliomas of spinal cord with H3K27M mutation are high-grade and the prognosis of patients is poor.
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Diffuse intrinsic pontine glioma (DIPG) is the main cause of brain tumor-related death among children. Until now, there is still a lack of effective therapy with prolonged overall survival for this disease. A typical strategy for preclinical cancer research is to find out the molecular differences between tumor tissue and para-tumor normal tissue, in order to identify potential therapeutic targets. Unfortunately, it is impossible to obtain normal tissue for DIPG because of the vital functions of the pons. Here we report the human fetal hindbrain-derived neural progenitor cells (pontine progenitor cells, PPCs) as normal control cells for DIPG. The PPCs not only harbored similar cell biological and molecular signatures as DIPG glioma stem cells, but also had the potential to be immortalized by the DIPG-specific mutation H3K27M in vitro. These findings provide researchers with a candidate normal control and a potential medicine carrier for preclinical research on DIPG.