Kakkar Aanchal, Kumar Anupam, Das Amitabha, Pathak Pankaj, Sharma Mehar C, Singh Manmohan, Suri Ashish, Sarkar Chitra, Suri Vaishali
Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.
Indian J Pathol Microbiol. 2015 Oct-Dec;58(4):433-8. doi: 10.4103/0377-4929.168852.
Meningiomas are the most common benign central nervous system tumors. However, a sizeable fraction recurs, irrespective of histological grade. No molecular marker is available for prediction of recurrence in these tumors.
We analyzed recurrent meningiomas with paired parent and recurrent tumors by fluorescence in situ hybridization for 1p36 and 14q32 deletion, AKT and SMO mutations by sequencing, and immunohistochemistry for GAB1, progesterone receptor (PR), p53, and MIB-1.
18 recurrent meningiomas (11 grade I, 3 grade II, 4 grade III) with their parent tumors (14 grade I, 2 grade II and 2 grade III) were identified. Overall, 61% of parent and 78% of recurrent meningiomas showed 1p/14q co-deletion. Notably, grade I parent tumors showed 1p/14q co-deletion in 64% cases while 82% of grade I recurrent tumors were co-deleted. AKT mutation was seen in two cases, in both parent and recurrent tumors. SMO mutations were absent. GAB1 was immunopositive in 80% parent and 56.3% recurrent tumors. MIB-1 labeling index (LI), PR and p53 expression did not appear to have any significant contribution in possible prediction of recurrence.
Identification of 1p/14q co-deletion in a significant proportion of histologically benign (grade I) meningiomas that recurred suggests its utility as a marker for prediction of recurrence. It appears to be a better predictive marker than MIB1-LI, PR and p53 expression. Recognition of AKT mutation in a subset of meningiomas may help identify patients that may benefit from PI3K/AKT pathway inhibitors, particularly among those at risk for development of recurrence, as determined by presence of 1p/14q co-deletion.
脑膜瘤是最常见的中枢神经系统良性肿瘤。然而，相当一部分会复发，无论组织学分级如何。目前尚无分子标志物可用于预测这些肿瘤的复发情况。
我们通过荧光原位杂交分析1p36和14q32缺失情况，对配对的原发性和复发性脑膜瘤进行测序检测AKT和SMO突变，并采用免疫组织化学检测GAB1、孕激素受体（PR）、p53和MIB-1。
共鉴定出18例复发性脑膜瘤（11例I级、3例II级、4例III级）及其原发性肿瘤（14例I级、2例II级和2例III级）。总体而言，61%的原发性和78%的复发性脑膜瘤显示1p/14q共缺失。值得注意的是，I级原发性肿瘤64%的病例显示1p/14q共缺失，而I级复发性肿瘤82%存在共缺失。在两例原发性和复发性肿瘤中均检测到AKT突变。未发现SMO突变。GAB1在80%的原发性肿瘤和56.3%的复发性肿瘤中呈免疫阳性。MIB-1标记指数（LI）、PR及p53表达在预测复发方面似乎没有显著作用。
在相当一部分复发的组织学良性（I级）脑膜瘤中鉴定出1p/14q共缺失，提示其可作为复发预测标志物。它似乎是比MIB1-LI、PR和p53表达更好的预测标志物。在一部分脑膜瘤中识别出AKT突变可能有助于确定哪些患者可能从PI3K/AKT通路抑制剂中获益，尤其是在那些根据1p/14q共缺失情况有复发风险的患者中。
