Uppar Alok Mohan, Sugur Harsha, Prabhuraj A R, Rao M Bhaskara, Devi B Indira, Sampath S, Arivazhagan A, Santosh Vani
Department of Neurosurgery, National Institute of Mental Health and Neurosciences, Hosur Road, Bangalore, 560029, India.
Department of Neuropathology, National Institute of Mental Health and Neurosciences, Hosur Road, Bangalore, 560029, India.
Childs Nerv Syst. 2019 Sep;35(9):1537-1545. doi: 10.1007/s00381-019-04222-z. Epub 2019 May 31.
Pediatric glioblastoma (pGBM) tumors have been identified as an entity distinct and different from the adult variety of GBM not only with respect to pathogenesis, genetics, and molecular alterations but also in clinical outcomes and overall survival. This study aims to evaluate the immunohistochemical profile of molecular markers in pediatric GBM and correlate them with clinical features and prognosis.
We retrospectively analyzed 29 pGBMs (age range 3 to 18 years), operated at our institute between 2009 and 2014, and evaluated their clinical and histopathological features along with the immunohistochemical expression of clinically relevant molecular markers: H3K27M, p53, ATRX, and IDH1 (R132H), and correlated their expression with clinical features. We further assessed the prognostic value of these markers in our cohort of patients.
The median overall survival (OS) of the cohort was 6.00 ± 0.882 months. The mean overall survival was 7.571 ± 1.118 months which was lower than in most studies. Preoperative Karnofsky Performance Score (KPS), extent of surgical resection, and adjuvant radiotherapy were found to be the clinical factors strongly influencing median survival (p < 0.05). Loss of ATRX expression was predominantly noted in hemispheric tumors (84%), while p53 staining was maximum in thalamic tumors (8 out of 9 cases). H3K27M mutant protein expression was noted in 8/9 thalamic tumors and 5/7 tumors in the brain stem-cerebellar-peduncular region. Patients with tumors showing H3K27M immunopositivity had the worst prognosis with a mean OS of 5 months ± 0.832 months, as against patients with H3K27M-immunonegative tumors, which was 10.143 ± 1.866 months(p = 0.006). Other markers like p53, ATRX, and IDH1 did not influence the prognosis in this patient cohort. ATRX loss of expression was associated with a better OS, with a trend to significance, and such an association has not been reported earlier.
Ours is one among the few studies from India describing the clinical parameters and evaluating the key immunohistochemical markers in pGBM and deriving their prognostic significance. The study reiterates the poor prognostic significance of H3K27M immunopositivity.
小儿胶质母细胞瘤(pGBM)已被确认为一种与成人型胶质母细胞瘤不同的实体,不仅在发病机制、遗传学和分子改变方面,而且在临床结果和总生存期方面都有所不同。本研究旨在评估小儿GBM中分子标志物的免疫组化特征,并将它们与临床特征和预后相关联。
我们回顾性分析了2009年至2014年间在我院接受手术的29例pGBM(年龄范围3至18岁),评估了它们的临床和组织病理学特征以及临床相关分子标志物H3K27M、p53、ATRX和异柠檬酸脱氢酶1(IDH1,R132H)的免疫组化表达,并将它们的表达与临床特征相关联。我们进一步评估了这些标志物在我们患者队列中的预后价值。
该队列的中位总生存期(OS)为6.00±0.882个月。平均总生存期为7.571±1.118个月,低于大多数研究。术前卡诺夫斯基功能状态评分(KPS)、手术切除范围和辅助放疗被发现是强烈影响中位生存期的临床因素(p<0.05)。ATRX表达缺失主要见于半球肿瘤(84%),而p53染色在丘脑肿瘤中最多见(9例中的8例)。H3K27M突变蛋白表达见于8/9例丘脑肿瘤和脑干-小脑-脑桥区域的5/7例肿瘤。显示H3K27M免疫阳性的肿瘤患者预后最差,平均OS为5个月±0.832个月,而H3K27M免疫阴性肿瘤患者的平均OS为10.143±1.866个月(p=0.006)。其他标志物如p53、ATRX和IDH1在该患者队列中不影响预后。ATRX表达缺失与较好的OS相关,有显著趋势,且这种关联此前未见报道。
我们的研究是印度少数描述pGBM临床参数、评估关键免疫组化标志物并得出其预后意义的研究之一。该研究重申了H3K27M免疫阳性的不良预后意义。