Battu Sudha, Kumar Anupam, Pathak Pankaj, Purkait Suvendu, Dhawan Linchi, Sharma Mehar C, Suri Ashish, Singh Manmohan, Sarkar Chitra, Suri Vaishali
Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.
Department of Neurosurgery, All India Institute of Medical Sciences, New Delhi, India.
Neuropathology. 2018 Feb;38(1):22-33. doi: 10.1111/neup.12426. Epub 2017 Sep 13.
Molecular and clinical characteristics of pediatric meningiomas are poorly defined. Therefore, we analyzed clinical, morphological and molecular profiles of pediatric meningiomas. Forty pediatric meningiomas from January 2002 to June 2015 were studied. 1p36, 14q32 and 22q-deletion were assessed by fluorescent in situ hybridization and mutations of most relevant exons of AKT, SMO, KLF4, TRAF and pTERT using sequencing. Expression of GAB1, stathmin, progesterone receptor (PR), p53 along with MIB-1 LI was examined using immunohistochemistry. There were 36 sporadic and four NF2 associated meningiomas. Among sporadic meningiomas, the majority (72.2%) of cases harbored 22q-deletion. Difference in frequency of combined 1p/14q deletion in Grade-I versus Grade-II/III tumors was not significant (13.7% vs 28.5%, P = 0.57). PR immunoreactivity was seen in 65.5% of Grade-I and 14.2% of Grade-II/III tumors (P = 0.03). The majority (97.2%) of meningiomas were immunonegative for p53. Stathmin and GAB co-expression was observed in 58.3% of cases. Notably, AKT, SMO, KLF4, TRAF7 (exon 17) and pTERT mutations were seen in none of the cases analyzed. 1p/14q codeletion was frequent in skull base as compared to non-skull base meningiomas (23% vs 11.1%, P = 0.37). All NF2 meningiomas harbored 22q-deletion and showed GAB and stathmin co-expression while none showed 1p/14q loss. Pediatric meningiomas share certain phenotypic and cytogenetic characteristics with adult counterparts, but GAB and stathmin co-expression in the majority of cases and non-significant difference in frequency of 1p/14q co-deletion between low- and high-grade meningiomas indicate an inherently aggressive nature. Characteristic AKT/SMO, KLF4/TRAF7 and pTERT genetic alterations seen in adults are distinctly absent in pediatric meningiomas.
儿童脑膜瘤的分子和临床特征尚不明确。因此，我们分析了儿童脑膜瘤的临床、形态学和分子特征。对2002年1月至2015年6月期间的40例儿童脑膜瘤进行了研究。通过荧光原位杂交评估1p36、14q32和22q缺失情况，并使用测序技术检测AKT、SMO、KLF4、TRAF和pTERT最相关外显子的突变。采用免疫组织化学方法检测GAB1、微管相关蛋白、孕激素受体（PR）、p53以及MIB-1标记指数的表达。其中有36例散发性脑膜瘤和4例与神经纤维瘤病2型（NF2）相关的脑膜瘤。在散发性脑膜瘤中，大多数病例（72.2%）存在22q缺失。I级与II/III级肿瘤中1p/14q联合缺失频率的差异无统计学意义（13.7%对28.5%，P = 0.57）。PR免疫反应性在I级肿瘤中见于65.5%，在II/III级肿瘤中见于14.2%（P = 0.03）。大多数脑膜瘤（97.2%）p53免疫阴性。58.3%的病例观察到微管相关蛋白和GAB共表达。值得注意的是，在所分析的病例中均未发现AKT、SMO、KLF4、TRAF7（外显子17）和pTERT突变。与非颅底脑膜瘤相比，1p/14q共缺失在颅底脑膜瘤中更为常见（23%对11.1%，P = 0.37）。所有NF2脑膜瘤均存在22q缺失，并显示GAB和微管相关蛋白共表达，而无一例显示1p/14q缺失。儿童脑膜瘤与成人脑膜瘤具有某些表型和细胞遗传学特征，但大多数病例中GAB和微管相关蛋白共表达以及低级别和高级别脑膜瘤中1p/14q共缺失频率无显著差异表明其具有内在的侵袭性。成人中所见的特征性AKT/SMO、KLF4/TRAF7和pTERT基因改变在儿童脑膜瘤中明显不存在。
