Geevar Tulasi, Pai Rekha, Chacko Geeta, Malepathi Karthik, Patel Bimal, John Jacob, Chacko Ari G, Balakrishnan Rajesh, John Subashini
Department of Pathology, Christian Medical College, Vellore, Tamil Nadu, India.
Department of Neurosurgery, Christian Medical College, Vellore, Tamil Nadu, India.
Neurol India. 2018 Nov-Dec;66(6):1726-1731. doi: 10.4103/0028-3886.246275.
The plethora of biomarkers available for the diagnosis and prognostication of gliomas has refined the classification of gliomas. The new World Health Organization (WHO) 2016 classification integrates the phenotypic and genotyping features for a more robust diagnosis.
Fifty gliomas with oligodendroglial morphology according to the WHO 2007 classification were analyzed for isocitrate dehydrogenase 1 and 2 (IDH1/2) mutations by polymerase chain reaction, 1p/19q status by fluorescent in situ hybridization (FISH), and IDH1 and X-linked alpha-thalassemia retardation (ATRX) expression by immunohistochemistry. Tumors were reclassified into oligodendrogliomas, astrocytomas, and glioblastomas (GBMs) according to the new "integrated" diagnostic approach.
30% of previously diagnosed oligodendrogliomas and almost 90% of oligoastrocytomas were reclassified as astrocytomas. Twenty gliomas showed 1p/19q co-deletion, while 18 gliomas showed polysomy of chromosome 1/19. Polysomy of chromosome 1/19 was significantly associated with astrocytic tumors (P ≤ 0.001). Loss of ATRX expression was seen in 20 of 23 WHO grade II/III astrocytomas and 3 of 7 GBMs. All WHO grade II and III gliomas in our cohort showed IDH1/2 mutations. Moreover, 4 of 7 GBMs showed the wild-type IDH1/2 mutation, and 2 of 3 GBMs which showed IDH1/2 mutations were secondary GBMs. There was no significant difference in progression-free and overall survival between WHO grade II and III gliomas, possibly because all these tumors showed IDH1/2 mutations. In multivariate analysis, only the WHO grade (grade IV versus II and III combined) was significantly associated with increased risk of recurrence and death (P = 0.016 and 0.02).
The new integrated diagnosis provides a more meaningful classification, removing the considerable subjectivity that existed previously.
可用于胶质瘤诊断和预后评估的生物标志物众多,这使得胶质瘤的分类更加精细。世界卫生组织(WHO)2016年的新分类整合了表型和基因分型特征,以实现更可靠的诊断。
对50例根据WHO 2007分类具有少突胶质细胞形态的胶质瘤进行分析,采用聚合酶链反应检测异柠檬酸脱氢酶1和2(IDH1/2)突变,荧光原位杂交(FISH)检测1p/19q状态,免疫组织化学检测IDH1和X连锁α地中海贫血智力发育迟缓(ATRX)表达。根据新的“综合”诊断方法,将肿瘤重新分类为少突胶质细胞瘤、星形细胞瘤和胶质母细胞瘤(GBM)。
30%先前诊断为少突胶质细胞瘤的病例以及近90%的少突星形细胞瘤被重新分类为星形细胞瘤。20例胶质瘤显示1p/19q共缺失,18例胶质瘤显示1号/19号染色体多体性。1号/19号染色体多体性与星形细胞肿瘤显著相关(P≤0.001)。在23例WHO二级/三级星形细胞瘤中有20例以及7例GBM中有3例出现ATRX表达缺失。我们队列中的所有WHO二级和三级胶质瘤均显示IDH1/2突变。此外,7例GBM中有4例显示IDH1/2野生型突变,3例显示IDH1/2突变的GBM中有2例为继发性GBM。WHO二级和三级胶质瘤在无进展生存期和总生存期方面无显著差异,可能是因为所有这些肿瘤均显示IDH1/2突变。在多变量分析中,只有WHO分级(四级与二级和三级合并)与复发和死亡风险增加显著相关(P = 0.016和0.02)。
新的综合诊断提供了更有意义的分类,消除了先前存在的相当大的主观性。