High p16 Expression Is Associated with Malignancy and Shorter Disease-Free Survival Time in Solitary Fibrous Tumor/Hemangiopericytoma
High p16 Expression Is Associated with Malignancy and Shorter Disease-Free Survival Time in Solitary Fibrous Tumor/Hemangiopericytoma
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DOI：
10.1055/s-0038-1669419
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发表时间：
2019-06-01
影响因子：
0.9
通讯作者：
Arkun, Knarik
中科院分区：
文献类型：
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作者：
Liang, Yuanxin;Heller, Robert S.;Arkun, Knarik
目的孤立性纤维瘤（SFT）和血管外皮细胞瘤（HPC）目前被分为沿着一类NAB 2-STAT 6融合的成纤维细胞间叶性肿瘤。这种融合作为组成型激活EGR 1的驱动突变，已知EGR 1参与p16通路。p16过表达与多发性间叶肿瘤的恶性程度和预后不良有关。作者试图研究p16免疫表达与SFT/HPC肿瘤的恶性程度和预后的关系。设计2002年至2016年在我们机构诊断的23例SFT/HPC肿瘤（中枢神经系统[CNS]：12例，非CNS：11例）被分为3个等级。分析了STAT 6、突触素、CD 56、嗜铬粒蛋白、SST 2A、EGFR 1、Ki 67和p16的微阵列免疫组织化学数据、分级和生存率。结果中枢神经系统SFT/HPC倾向于恶性（3级; 67%与18%，p =0.036），并且比非中枢神经系统肿瘤更有可能表达突触素（33%与0%，p =0.035）。p16过表达（免疫阳性50%肿瘤细胞）与恶性（3级）肿瘤相关，作为恶性肿瘤的预测标志物，其敏感性为70%（7/10），特异性为77%（10/13）。p16低表达的SFT/HPC患者的无瘤生存期（中位生存期>113个月）明显长于p16高表达的SFT/HPC患者（中位生存期=30个月，p =0.045）。在我们的研究队列中，高p16表达也与SFT/HPC肿瘤的恶性程度和较短的无病生存期相关。在临床上，p16过表达可作为肿瘤恶性程度和预后的预测指标，也可作为一种可能的治疗靶点。
Objective Solitary fibrous tumors (SFT) and hemangiopericytomas (HPC) are now classified along a single spectrum of fibroblastic mesenchymal tumors with NAB2-STAT6 fusion. This fusion acts as a driver mutation that constitutively activates EGR1, which is known to be involved in the p16 pathway. Overexpression of p16 is associated with malignancy and worse prognosis in multiple mesenchymal tumors. The authors sought to investigate p16 immunoexpression in association with malignancy and prognosis of SFT/HPC tumors.Design Twenty-three SFT/HPC tumors (central nervous system [CNS]: 12, non CNS: 11) diagnosed at our institution from 2002 to 2016 were assigned into 3 grades. Data from microarray immunohistochemistry for STAT6, synaptophysin, CD56, chromogranin, SST2A, EGR1, Ki67, and p16, grade and survival were analyzed.Results CNS SFT/HPCs tend to be malignant (grade 3; 67 vs. 18%, p =0.036) and more likely to express synaptophysin (33 vs. 0%, p =0.035) than non CNS tumors. Overexpression of p16 (immunopositivity 50% tumor cells) was associated with malignant (grade 3) tumors, and has a sensitivity of 70% (7/10), and a specificity of 77% (10/13), as a predictive marker for malignancy. SFT/HPC patients with low p16 expression demonstrated significantly longer disease-free survival time (median survival>113 months) than those with high p16 expression (median survival=30 months, p =0.045).Conclusions SFT/HPCs in the CNS are more likely to be malignant than the tumors in other sites. High p16 expression is also associated with malignancy and shorter disease-free survival time in SFT/HPC tumors in our study cohort. Clinically, p16 overexpression can be used as predictive marker for malignancy and prognosis and a possible therapeutic target.