Elsers Dalia, Temerik Doaa F, Attia Alia M, Hadia A, Hussien Marwa T
Department of Pathology, Faculty of Medicine, Assiut University, Assiut, Egypt.
Department of Clinical Pathology, South Egypt Cancer Institute, Assiut University, Assiut, Egypt.
J Pathol Transl Med. 2021 May;55(3):212-224. doi: 10.4132/jptm.2021.03.15. Epub 2021 May 11.
Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase that is expressed in the developing central and peripheral nervous systems during embryogenesis. Human telomerase reverse transcriptase (h-TERT) protein resumption is the main process of preservation of telomeres that maintains DNA integrity. The present study aims to evaluate the prognostic role of ALK-1 and h-TERT protein expression and their correlation with ALK gene alterations in glioblastoma multiforme (GBM).
The current study is a retrospective study on a cohort of patients with GBM (n = 53) that attempted to detect ALK gene alterations using fluorescence in situ hybridization. ALK-1 and h-TERT proteins were evaluated using immunohistochemistry.
Score 3 ALK-1 expression was significantly associated with male sex, tumor multiplicity, Ki labeling index (Ki LI), and type of therapeutic modality. Score 3 h-TERT expression exhibited a significant association with Ki LI. ALK gene amplifications (ALK-A) were significantly associated with increased Ki LI and therapeutic modalities. Score 3 ALK-1 protein expression, score 3 h-TERT protein expression, and ALK-A were associated with poor overall survival (OS) and progression-free survival (PFS). Multivariate analysis for OS revealed that ALK gene alterations were an independent prognostic factor for OS and PFS.
High protein expression of both ALK-1 and h-TERT, as well as ALK-A had a poor impact on the prognosis of GBM. Further studies are needed to establish the underlying mechanisms.
间变性淋巴瘤激酶（ALK）是一种受体酪氨酸激酶，在胚胎发育过程中于中枢和外周神经系统发育阶段表达。人端粒酶逆转录酶（h-TERT）蛋白的恢复是维持端粒从而保持DNA完整性的主要过程。本研究旨在评估ALK-1和h-TERT蛋白表达在多形性胶质母细胞瘤（GBM）中的预后作用及其与ALK基因改变的相关性。
本研究是一项对GBM患者队列（n = 53）的回顾性研究，试图通过荧光原位杂交检测ALK基因改变。使用免疫组织化学评估ALK-1和h-TERT蛋白。
ALK-1表达评分为3与男性、肿瘤多灶性、Ki标记指数（Ki LI）和治疗方式类型显著相关。h-TERT表达评分为3与Ki LI显著相关。ALK基因扩增（ALK-A）与Ki LI增加和治疗方式显著相关。ALK-1蛋白表达评分为3、h-TERT蛋白表达评分为3和ALK-A与总生存期（OS）和无进展生存期（PFS）较差相关。OS的多变量分析显示，ALK基因改变是OS和PFS的独立预后因素。
ALK-1和h-TERT的高蛋白表达以及ALK-A对GBM的预后有不良影响。需要进一步研究以确定潜在机制。
