Expression of Anaplastic Lymphoma Kinase in Astrocytic Tumors (Histopathological and Immunohistochemical Study)

Abstract

BACKGROUND: Astrocytic tumors are the most common primary brain tumors. Glioblastoma is the most common astrocytic tumor representing the highest World Health Organization (WHO) grade (WHO grade IV) with poor prognosis and short survival time. Anaplastic lymphoma kinase (ALK) has a role in embryonic central nervous system development. ALK receptor is thought to contribute to nervous system function, repair, and metabolic homeostasis and is expressed in high-grade tumors like anaplastic large cell lymphoma that makes it a potential target for therapeutic intervention. AIM: This work aimed to examine the immunohistochemical expression of ALK in astrocytic tumors and its correlation with age, sex, clinical presentation, location, laterality, recurrence, and WHO grade to implicate possible therapeutic potential. METHODS: This retrospective study was conducted on sixty cases of archived, formalin-fixed, paraffin-embedded tissue blocks that included different subtypes and grades of astrocytic tumors. Immunohistochemistry using ALK monoclonal antibody was performed using a standard avidin-biotin-peroxidase system. RESULTS: Of the sixty cases, 57 (95%) cases were negative for ALK, while three (5%) cases are positive for ALK; all showed the strong intensity of expression. No statistically significant association was found between ALK expression and astrocytic tumors in addition to other clinical variables of the studied tumors. CONCLUSIONS: Most cases of astrocytic tumors showed negative ALK expression apart from three positive cases seen in higher WHO grades, especially gliosarcoma. The high number of negative cases for ALK in our study group suggests that ALK expression is not associated with a prognostic significance toward astrocytic tumors whatever its grade.

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

“…In our study, higher ALK-1 immunoexpression was noted in the tumors larger than the mean size (13/16); a finding in harmony with Elsers et al 2021 [ 18 ], and Hakeem et al 2021 [ 19 ]. No statistically significant correlation was be detected between ALK-1 expression and the histologic variants of the tumors in our study.…”

“…No statistically significant correlation was be detected between ALK-1 expression and the histologic variants of the tumors in our study. Regarding the association between tumor recurrence and ALK-1 immunoexpression, we observed positivity in only one recurrent case (8.3%), and the association was not statistically significant, which aligns with the findings of Hakeem et al 2021 [ 19 ]. However, Azab 2023 [ 21 ] demonstrated a significant correlation between tumor recurrence and the ALK staining score of tumors.…”

“…This difference might be ascribed to variations in environmental factors and sample size. As for the correlation of ALK-1 immunoexpression with the gender of the studied cases, we reported higher expression in males (14/16); a finding consistent with Karagkounis et al 2017 [ 17 ], Elsers et al (021 [ 18 ], and Hakeem et al 2021 [ 19 ]. The established male predominance in GBs might clarify those concordant findings.…”

“…In the present study, ALK-1 expression was higher in cases older than the mean age compared to those younger than the mean age, disagreeing with Ferguson et al 2016 [ 20 ], yet, consistent with Karagkounis et al 2017 [ 17 ], Elsers et al 2021 [ 18 ], Hakeem et al 2021 [ 19 ] as they all noted more frequent ALK overexpression in older cases. This difference might be ascribed to variations in environmental factors and sample size.…”

“…However, Chiba et al 2017 [ 14 ], Karagkounis et al 2017 [ 17 ], Elsers et al 2021 [ 18 ] showed much higher positivity rates; 84.9%, 49.2% & 70.6% respectively. Conversely, Hakeem et al 2021 [ 19 ] showed ALK-1 positivity in only 3 of their 60 studied astrocytoma cases, 2 of which were grade 4. These different findings can be attributed to tissue fixation, immunohistochemistry methodology, and cut-offs used for positivity.…”