Department of Oncology, AUSL Bologna, Bologna, Italy.
Department of Pharmacy and Biotechnology (FaBIT) - Molecular Pathology Laboratory, University of Bologna, Bologna, Italy.
Pathol Res Pract. 2021 May;221:153447. doi: 10.1016/j.prp.2021.153447. Epub 2021 Apr 15.
anaplastic lymphoma kinase (ALK) overexpression and gene alterations have been detected in several malignancies, with prognostic and therapeutic implications. However, few studies investigated the correlation between ALK altered expression and prognosis in patients with glioblastoma (GBM).
We performed an evaluation of ALK overexpression and structural/quantitative chromosome alterations through immune-histochemical assay (IHC with D5F3 antibody) and fluorescent in situ hybridization (FISH) in patients with isocitrate dehydrogenase (IDH) wild type (wt) GBM. Assuming an ALK overexpression in 20 % of patients we planned a sample of 44 patients to achieve a probability of 90 % to include from 10 % to 30 % of patients with ALK alterations.
We evaluated 44 patients with IDH wt GBM, treated in our institution and dead due to GBM progression in 2017. ALK overexpression obtained by a composed score (the product of IHC intensity staining and rate of positive cells) was observed in 19 (43 %) patients. FISH analysis showed that 11 patients (25 %) had gene deletion, 2 patients (4.5 %) had monosomy and one patient (2.3 %) presented polysomy. Only one patient (2.3 %) demonstrated ALK rearrangement. There was no statistical difference in median OS between patients with ALK-positive (mOS = 18.9 months) and ALK-negative IHC (mOS = 18.0 months).
We identified some rare previously unreported alterations of ALK gene in patients with IDH wt GBM. In these patients, the ALK overexpression does not influences survival.
在多种恶性肿瘤中已经检测到间变性淋巴瘤激酶（ALK）的过表达和基因改变，这些改变具有预后和治疗意义。然而，很少有研究调查 ALK 改变表达与胶质母细胞瘤（GBM）患者预后之间的相关性。
我们通过免疫组织化学检测（使用 D5F3 抗体）和荧光原位杂交（FISH）对 IDH 野生型（wt）GBM 患者的 ALK 过表达和结构/定量染色体改变进行了评估。假设 20%的患者存在 ALK 过表达，我们计划对 44 例患者进行样本分析，以达到 90%的概率包括 10%至 30%的存在 ALK 改变的患者。
我们评估了 44 例 IDH wt GBM 患者，这些患者在我们的机构接受治疗，2017 年因 GBM 进展而死亡。通过综合评分（免疫组化强度染色和阳性细胞率的乘积）观察到 19 例（43%）患者存在 ALK 过表达。FISH 分析显示 11 例患者（25%）存在基因缺失，2 例患者（4.5%）存在单体性，1 例患者（2.3%）存在多倍体。仅 1 例患者（2.3%）显示 ALK 重排。ALK 阳性（mOS=18.9 个月）和 ALK 阴性免疫组化（mOS=18.0 个月）患者的中位 OS 无统计学差异。
我们在 IDH wt GBM 患者中发现了一些先前未报道的 ALK 基因罕见改变。在这些患者中，ALK 过表达并不影响生存。
