Sarma Susmita, Khonglah Yookarin, Mishra Jaya, Kakati Arindom, Phukan Pranjal
Department of Pathology, North Eastern Indira Gandhi Regional Institute of Health and Medical Sciences, Shillong, Meghalaya, India.
Department of Neurosurgery, North Eastern Indira Gandhi Regional Institute of Health and Medical Sciences, Shillong, Meghalaya, India.
J Family Med Prim Care. 2021 Mar;10(3):1341-1346. doi: 10.4103/jfmpc.jfmpc_1963_20. Epub 2021 Apr 8.
Gliomas account for 45% of all intracranial tumors. Newer technologies have allowed deeper genetic and epigenetic analysis leading to the discovery of IDH (Isocitrate dehydrogenase) mutations and their association with ATRX (alpha-thalassemia/mental retardation syndrome X-linked) and p53, for better diagnosis and prognosis. In this study, we analysed their expression and correlated with various clinicopathological parameters. A follow up to prognosticate gliomas based on the molecular findings is also attempted.
During last 5 years both retrospective and prospective cases were included in the study. Immunohistochemistry for IDH1, ATRX, and p53 was done and reported based on intensity and percentage of tumor cells expressing the markers.
A total of 53 cases of gliomas were included, excluding primary glioblastomas and ependymomas. The patient's age ranged from 10 to 53 years. The male to female ratio was 1.3:1. IDH1 positivity was seen in 88% of diffuse astrocytoma, 80% of anaplastic astrocytoma, 90% of oligodendroglioma, 60% of anaplastic oligodendroglioma, and 54% of glioblastoma. A significant association was seen between positive IDH1 expression and low-grade gliomas ( = 0.028). A combined analysis of expression of IDH1 and ATRX versus IDH1, ATRX, and p53 with WHO grade showed a statistically significant association. A follow-up of 32 patients was available. Out of 24 IDH1+ (positive) cases, 22 patients had a median survival of 21.5 months (92%). Out of 8 IDH1- (negative) cases, 5 had a median survival of 15.8 months (62%).
Gliomas expressing IDH1 mutation show improved survival of patients. Combined analysis of IDH1, ATRX, and p53 has diagnostic and prognostic significance. For routine cases of gliomas, a combination of IDH1 and ATRX are sufficient; however, the use of p53 is recommended for further prognostication and for possible targeted therapy in the future.
胶质瘤占所有颅内肿瘤的45%。新技术使得更深入的基因和表观遗传学分析成为可能，从而发现了异柠檬酸脱氢酶（IDH）突变及其与α地中海贫血/智力发育迟缓综合征X连锁（ATRX）和p53的关联，以实现更好的诊断和预后评估。在本研究中，我们分析了它们的表达情况，并将其与各种临床病理参数进行关联分析。还尝试根据分子研究结果对胶质瘤进行预后预测。
在过去5年中，研究纳入了回顾性和前瞻性病例。对IDH1、ATRX和p53进行免疫组织化学检测，并根据表达标志物的肿瘤细胞强度和百分比进行报告。
共纳入53例胶质瘤病例，排除原发性胶质母细胞瘤和室管膜瘤。患者年龄在10至53岁之间。男女比例为1.3:1。在88%的弥漫性星形细胞瘤、80%的间变性星形细胞瘤、90%的少突胶质细胞瘤、60%的间变性少突胶质细胞瘤和54%的胶质母细胞瘤中观察到IDH1阳性。IDH1阳性表达与低级别胶质瘤之间存在显著关联（P = 0.028）。IDH1和ATRX表达与IDH1、ATRX和p53表达联合分析与世界卫生组织分级显示出统计学上的显著关联。对32例患者进行了随访。在24例IDH1阳性病例中，22例患者的中位生存期为21.5个月（92%）。在8例IDH1阴性病例中，5例患者的中位生存期为15.8个月（62%）。
表达IDH1突变的胶质瘤患者生存期得到改善。IDH1、ATRX和p53的联合分析具有诊断和预后意义。对于胶质瘤的常规病例，IDH1和ATRX的联合检测就足够了；然而，建议使用p53进行进一步的预后评估以及未来可能的靶向治疗。
