Evaluation of Immunohistochemical Expression of ALK-1 in Gliomas, WHO Grade 4 and Its Correlation with IDH1-R132H Mutation Status.

BACKGROUND: Glioblastoma (GB), a grade 4 glioma is the most common primary malignant brain tumor in adults. Recently, the mutation status of isocitrate dehydrogenase (IDH) has been crucial in the treatment of GB. IDH mutant cases display a more favorable prognosis than IDH-wild type ones. The anaplastic lymphoma kinase (ALK) is expressed as a receptor tyrosine kinase in both the developing central and peripheral nervous systems. Increasing lines of evidence suggest that ALK is over-expressed in GB and represents a potential therapeutic target. OBJECTIVES: The goal of the current study was to investigate ALK-1 immunohistochemical expression in gliomas, grade 4, besides its correlation with IDH1-R132H mutation status and the clinicopathological parameters of the tumors. MATERIAL AND METHODS: Seventy cases of gliomas, grade 4 were tested for immunohistochemical expression of ALK-1 & IDH1-R132H in the tumor cells. RESULTS: ALK-1 immunoexpression was detected in 22.9% of our cases and IDH1-R132H mutation was detected in 12.9% of them. ALK-1 expression (100%) was only detected in the more aggressive IDH R132H-negative GBs. ALK-1 expression was also noted in the larger-sized tumors, more in males and patients older than the mean age.  Conclusion: Our results suggest that mutations in ALK-1 may predict a more dismal prognosis since ALK expression was only noted in IDH-R132H negative GBs known to have a considerably poorer outcome compared to IDH-R132H mutant cases. GBs with detectable ALK-protein expression could potentially experience substantial clinical advantages through the utilization of newly introduced ALK inhibitors allowing personalized treatment to a subset of patients. Hence, future studies targeting ALK in IDH wildtype Glioblastomas including clinical trials on larger scales are recommended.

The Pathological Evaluation of Autophagy-Related Protein (LC3B) and Its Association with the Infiltration of Immune Cells in Glioma.

BACKGROUND: Tumor cell autophagy can influence cellular immunity by participation in the recognition and modification of tumor-related antigens. OBJECTIVES: The objective of this study was to evaluate the immunohistochemical expression of the autophagy-related marker; light chain 3B (LC3B) in tumor cells and the assessment of T lymphocytes by a cluster of differentiation 3 (CD3) in gliomas, and to correlate them with the available clinic-pathological variables in glioma patients. MATERIALS AND METHODS: Immunohistochemical staining for LC3B and CD3 was performed on 60 paraffin-embedded glioma tissue. LC3B immunoreactivity score of 0-6 was designated negative, and those scoring 7-12 were considered positive. The median level of CD3 positive T lymphocytes was calculated for both high and low-grade gliomas. In low-grade gliomas, the CD3 expressing T lymphocytes equal to or more than 2.6, were considered positive while in high-grade gliomas, those equal to or more than 16 were considered positive. RESULTS: LC3B expression in tumor cells was detected in 24/60 (40%) of gliomas. Expression of LC3B was significantly more frequent in high-grade gliomas (23/33, 69.7%) compared to low grade ones (1/27, 5%), (p value= 0.000). LC3B expression was correlated with the patients age (P value= 0.047) & histological variants (P value= 0.000). CD3 positive T lymphocytes were significantly more prominent in high-grade gliomas (25/33 , 41.7%)  than low-grade ones (2/27, 3.3%), (P value= 0.001). A significant association was noted between CD3 expression and the patients age (P value= 0.003), sex (P value: 0.035) and histological variants (P value= 0.001). LC3B expression in tumor cells was significantly correlated with CD3 positive T lymphocytes (P value: 0.000). CONCLUSION: Autophagic activity of tumor cells and T lymphocyte infiltrates were reported more in high-grade gliomas compared to low-grade ones, giving high-grade gliomas the chance in autophagy target therapy & immunotherapy.