Liang Yuanxin, Heller Robert S, Wu Julian K, Heilman Carl B, Tischler Arthur S, Arkun Knarik
Department of Pathology and Laboratory Medicine, Tufts Medical Center and Tufts University School of Medicine, Boston, Massachusetts, United States.
Department of Neurosurgery, Tufts Medical Center and Tufts University School of Medicine, Boston, Massachusetts, United States.
J Neurol Surg B Skull Base. 2019 Jun;80(3):232-238. doi: 10.1055/s-0038-1669419. Epub 2018 Aug 21.
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. 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. CNS SFT/HPCs tend to be malignant (grade 3; 67 vs. 18%, = 0.036) and more likely to express synaptophysin (33 vs. 0%, = 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, = 0.045). 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.
孤立性纤维瘤（SFT）和血管外皮细胞瘤（HPC）现被归为具有NAB2 - STAT6融合的单一谱系的成纤维细胞间叶性肿瘤。这种融合作为一种驱动突变，持续激活已知参与p16通路的EGR1。p16的过表达与多种间叶性肿瘤的恶性程度及较差预后相关。作者旨在研究p16免疫表达与SFT/HPC肿瘤的恶性程度及预后的关系。
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STAT6、突触素、CD56、嗜铬粒蛋白、SST2A、EGR1、Ki67和p16的微阵列免疫组化数据、等级及生存情况。
与非CNS肿瘤相比，CNS的SFT/HPC更倾向于恶性（3级；67%对18%，P = 0.036）且更可能表达突触素（33%对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，作为恶性程度的预测标志物，其敏感性为70%（7/10），特异性为77%（10/13）。低p16表达的SFT/HPC患者的无病生存期（中位生存期>113个月）显著长于高p16表达患者（中位生存期 = 30个月，P = 0.045）。
在我们的研究队列中，CNS的SFT/HPC比其他部位的肿瘤更易发生恶性变。高p16表达也与SFT/HPC肿瘤的恶性程度及较短的无病生存期相关。临床上，p16过表达可作为恶性程度和预后的预测标志物以及可能的治疗靶点。
