Kiviniemi Aida, Gardberg Maria, Kivinen Katri, Posti Jussi P, Vuorinen Ville, Sipilä Jussi, Rahi Melissa, Sankinen Matti, Minn Heikki
Department of Radiology, Medical Imaging Center of Southwest Finland, Turku University Hospital and University of Turku, Turku, Finland.
Turku PET Center, Turku University Hospital and University of Turku, Turku, Finland.
Oncotarget. 2017 Jul 25;8(30):49123-49132. doi: 10.18632/oncotarget.17097.
Somatostatin receptor subtype 2A (SSTR2A) is a potential therapeutic target in gliomas. Data on SSTR2A expression in different glioma entities, however, is particularly conflicting. Our objective was to characterize SSTR2A status and explore its impact on survival in gliomas classified according to the specific molecular signatures of the updated WHO classification. In total, 184 glioma samples were retrospectively analyzed for SSTR2A expression using immunohistochemistry with monoclonal antibody UMB-1. Double staining with CD68 was used to exclude microglia and macrophages from analyses. SSTR2A staining intensity and its localization in tumor cells was evaluated and correlated with glioma entities and survival. Diagnoses included 101 glioblastomas (93 isocitrate dehydrogenase (IDH) -wildtype, 3 IDH-mutant, 5 not otherwise specified (NOS)), 60 astrocytomas (22 IDH-wildtype, 37 IDH-mutant, 1 NOS), and 23 oligodendrogliomas (19 IDH-mutant and 1p/19q-codeleted, 4 NOS). SSTR2A expression significantly associated with oligodendrogliomas (79% SSTR2A positive) compared to IDH-mutant or IDH-wildtype astrocytomas (27% and 23% SSTR2A positive, respectively), and especially glioblastomas of which only 13% were SSTR2A positive (p < 0.001, Fisher's exact test). The staining pattern in glioblastomas was patchy whereas more homogeneous membranous and cytoplasmic staining was detected in oligodendrogliomas. Positive SSTR2A was related to longer overall survival in grade II and III gliomas (HR 2.7, CI 1.2-5.8, p = 0.013). In conclusion, SSTR2A expression is infrequent in astrocytomas and negative in the majority of glioblastomas where it is of no prognostic significance. In contrast, oligodendrogliomas show intense membranous and cytoplasmic SSTR2A expression, which carries potential diagnostic, prognostic, and therapeutic value.
生长抑素受体2A亚型(SSTR2A)是神经胶质瘤潜在的治疗靶点。然而,关于不同神经胶质瘤实体中SSTR2A表达的数据存在特别大的冲突。我们的目的是根据世界卫生组织(WHO)更新分类的特定分子特征,对神经胶质瘤中的SSTR2A状态进行特征描述,并探讨其对生存的影响。总共对184例神经胶质瘤样本进行回顾性分析,使用单克隆抗体UMB-1通过免疫组织化学检测SSTR2A表达。采用CD68双重染色以在分析中排除小胶质细胞和巨噬细胞。评估SSTR2A染色强度及其在肿瘤细胞中的定位,并将其与神经胶质瘤实体及生存情况相关联。诊断包括101例胶质母细胞瘤(93例异柠檬酸脱氢酶(IDH)野生型、3例IDH突变型、5例未另行指定(NOS))、60例星形细胞瘤(22例IDH野生型、37例IDH突变型、1例NOS)和23例少突胶质细胞瘤(19例IDH突变型且1p/19q共缺失、4例NOS)。与IDH突变型或IDH野生型星形细胞瘤(分别为27%和23%的SSTR2A阳性)相比,SSTR2A表达与少突胶质细胞瘤显著相关(79%的SSTR2A阳性),尤其是胶质母细胞瘤,其中只有13%为SSTR2A阳性(p<0.001,Fisher精确检验)。胶质母细胞瘤的染色模式呈斑片状,而少突胶质细胞瘤中检测到更均匀的膜性和细胞质染色。SSTR2A阳性与II级和III级神经胶质瘤的总生存期延长相关(风险比2.7,置信区间1.2 - 5.8,p = 0.013)。总之,SSTR2A表达在星形细胞瘤中少见,在大多数胶质母细胞瘤中为阴性,且无预后意义。相比之下,少突胶质细胞瘤显示出强烈的膜性和细胞质SSTR2A表达,具有潜在的诊断、预后和治疗价值。