Department of Molecular Pathology, Markusovszky University Teaching Hospital, Szombathely.
Institute of Laboratory Medicine, Clinical Center and the Szentagothai Research Center, University of Pécs, School of Medicine, Pécs.
Ideggyogy Sz. 2021 Sep 30;74(9-10):349-355. doi: 10.18071/isz.74.0349.
Aberrant activation of the Wnt pathway contributes to differentiation and maintenance of cancer stem cells underlying gliomagenesis. The aim of our research was to determine as to what degrees some Wnt markers are expressed in gliomas of different grades, lineages and molecular subtypes.
Nine grade II, 10 grade III and 72 grade IV surgically removed, formalin-fixed paraffin-embedded glioma specimens were included. Mutation status of IDH1 codon 132 was defined by immunohistochemistry and pyrosequencing in all tumors. Grade II and III astrocytic and oligodendroglial tumors were further tested for the expression of p53 and ATRX by immunohistochemistry, and codeletion of 1p19q by fluorescent in situ hybridization. Expression levels of the non-canonical Wnt5a and Fzd2, and the canonical Wnt3a and beta-catenin Wnt pathway markers were determined by immunohistochemistry, and compared between subgroups stratified according to grade, lineage and the presence or absence of IDH1 R132H/C mutations.
In the normal brain - grade II-IV glioma comparisons, a gradual increase was observed for the expressions of Wnt5a, Wnt3a, Fzd2 and beta-catenin. In the astroglial and oligodendroglial lineages of grade II and III gliomas, only the Wnt5a expression was significantly higher in the astroglial subgroup. Stratification according to the IDH1 status resulted in a significant increase of the Wnt3 expression in the wild type grade II-IV gliomas.
These data extend previous observations and show a correlation of Wnt pathway activity with glioma grade. Further investigations of the Wnt marker expression regulation according to glioma lineage or IDH gene mutational status are in progress by using more exact molecular approaches.
Wnt 通路的异常激活有助于胶质瘤发生的肿瘤干细胞的分化和维持。我们研究的目的是确定不同级别、谱系和分子亚型的胶质瘤中某些 Wnt 标志物的表达程度。
纳入了 9 例 2 级、10 例 3 级和 72 例 4 级手术切除的福尔马林固定石蜡包埋的胶质瘤标本。所有肿瘤均通过免疫组化和焦磷酸测序检测 IDH1 密码子 132 的突变状态。2 级和 3 级星形细胞和少突胶质细胞瘤进一步通过免疫组化检测 p53 和 ATRX 的表达，并通过荧光原位杂交检测 1p19q 的缺失。通过免疫组化检测非经典 Wnt5a 和 Fzd2 以及经典 Wnt3a 和 β-连环蛋白 Wnt 通路标志物的表达水平，并根据分级、谱系以及 IDH1 R132H/C 突变的存在与否对亚组进行分层比较。
在正常大脑-2 级-4 级胶质瘤的比较中，Wnt5a、Wnt3a、Fzd2 和 β-连环蛋白的表达逐渐增加。在 2 级和 3 级星形细胞瘤和少突胶质细胞瘤中，仅星形细胞瘤亚组的 Wnt5a 表达显著升高。根据 IDH1 状态分层，野生型 2 级-4 级胶质瘤的 Wnt3 表达显著增加。
这些数据扩展了以前的观察结果，表明 Wnt 通路活性与胶质瘤分级相关。我们正在使用更精确的分子方法进一步研究根据胶质瘤谱系或 IDH 基因突变状态的 Wnt 标志物表达调控。
