Departments of Pathology.
Neurosurgery.
Appl Immunohistochem Mol Morphol. 2022 Jul 1;30(6):410-417. doi: 10.1097/PAI.0000000000001038. Epub 2022 Jun 17.
IDH wild-type (wt) grade 2/3 astrocytomas are a heterogenous group of tumors with disparate clinical and molecular profiles. cIMPACT-NOW recommendations incorporated in the new 2021 World Health Organization (WHO) Classification of Central Nervous System (CNS) Tumors urge minimal molecular criteria to identify a subset that has an aggressive clinical course similar to IDH -wt glioblastomas (GBMs). This paper describes the use of a panel of molecular markers to reclassify IDH -wt grade 2/3 diffuse astrocytic gliomas (DAGs) and study median overall survival concerning for to IDH -wt GBMs in the Indian cohort. IDH -wt astrocytic gliomas (grades 2, 3, and 4) confirmed by IDHR132H immunohistochemistry and IDH1/2 gene sequencing, 1p/19q non-codeleted with no H3F3A mutations were included. TERT promoter mutation by Sanger sequencing, epidermal growth factor receptor amplification, and whole chromosome 7 gain and chromosome 10 loss by fluorescence in situ hybridization was assessed and findings correlated with clinical and demographic profiles. The molecular profile of 53 IDH -wt DAGs (grade 2: 31, grade 3: 22) was analyzed. Eleven cases (grade 2: 8, grade 3: 3) (20.75%) were reclassified as IDH -wt GBMs, WHO grade 4 ( TERT promoter mutation in 17%, epidermal growth factor receptor amplification in 5.5%, and whole chromosome 7 gain and chromosome 10 loss in 2%). Molecular GBMs were predominantly frontal (54.5%) with a mean age of 36 years and median overall survival equivalent to IDH -wt GBMs (18 vs. 19 mo; P =0.235). Among grade 2/3 DAGs not harboring these alterations, significantly better survival was observed for grade 2 versus grade 3 DAGs (25 vs. 16 mo; P =0.002). Through the incorporation of a panel of molecular markers, a subset of IDH -wt grade 2 DAGs can be stratified into molecular grade 4 tumors with prognostic and therapeutic implications. However, IDH -wt grade 3 DAGs behave like GBMs irrespective of molecular profile.
IDH 野生型（wt）2/3 级星形细胞瘤是一组具有不同临床和分子特征的异质性肿瘤。新的 2021 年世界卫生组织（WHO）中枢神经系统（CNS）肿瘤分类中纳入了 cIMPACT-NOW 建议，要求采用最小的分子标准来确定一组具有类似于 IDH-wt 胶质母细胞瘤（GBM）侵袭性临床病程的肿瘤亚群。本文描述了使用一组分子标志物重新分类 IDH-wt 2/3 级弥漫性星形细胞瘤（DAG），并研究了印度队列中 IDH-wt GBM 的中位总生存期。通过 IDHR132H 免疫组织化学和 IDH1/2 基因测序证实 IDH-wt 星形细胞瘤（2 级、3 级和 4 级），1p/19q 非缺失且无 H3F3A 突变。通过 Sanger 测序评估 TERT 启动子突变、表皮生长因子受体扩增以及通过荧光原位杂交评估整条 7 号染色体获得和 10 号染色体丢失，并将结果与临床和人口统计学特征相关联。对 53 例 IDH-wt DAG（2 级：31 例，3 级：22 例）的分子谱进行了分析。11 例（2 级：8 例，3 级：3 例）（20.75%）被重新分类为 IDH-wt GBM，WHO 分级 4（TERT 启动子突变占 17%，表皮生长因子受体扩增占 5.5%，整条 7 号染色体获得和 10 号染色体丢失占 2%）。分子 GBM 主要位于额部（54.5%），平均年龄为 36 岁，中位总生存期与 IDH-wt GBM 相当（18 与 19 个月；P=0.235）。在未携带这些改变的 2/3 级 DAG 中，2 级 DAG 的生存情况明显优于 3 级 DAG（25 与 16 个月；P=0.002）。通过纳入一组分子标志物，可以将 IDH-wt 2 级 DAG 的亚组分层为具有预后和治疗意义的分子分级 4 肿瘤。然而，无论分子谱如何，IDH-wt 3 级 DAG 均表现为 GBM。
