Ülgen Ege, Bektaşoğlu Pınar Kuru, Sav M Aydın, Can Özge, Danyeli Ayça Erşen, Hızal Deniz Baycın, Pamir M Necmettin, Özduman Koray
Department of Biostatistics and Medical Informatics, School of Medicine, Acıbadem Mehmet Ali Aydınlar University, Istanbul, Turkey.
Department of Neurosurgery, Turkish Ministry of Health, University of Health Sciences, Fatih Sultan Mehmet Education and Research Hospital, Istanbul, Turkey; Department of Physiology, Marmara University School of Medicine, Istanbul, Turkey.
World Neurosurg. 2019 Mar;123:e520-e535. doi: 10.1016/j.wneu.2018.11.201. Epub 2018 Nov 29.
Meningiomas are heterogeneous, with differences in anatomical, histopathological, and clinical characteristics. Such spatial variability in meningioma biology is thought to result from differences in the expression of critical developmental regulators. We hypothesized that the variability in meningioma biology would follow gradients such as in embryology and tested a cohort of 366 meningiomas for histopathological and immunohistochemical gradients.
The medical records from 366 patients treated for meningiomas from 2003 to 2016 were retrospectively analyzed for age, gender, anatomical localization, recurrence-free survival, overall survival, histopathological diagnosis, and immunohistochemistry findings for 6 markers: epithelial membrane antigen (EMA), progesterone receptor (PR), CD34, S100, p53, and Ki-67 labeling index.
EMA, PR, S100, p53, and CD34 were expressed in 94%, 73%, 49%, 26%, and 23% of the tumors, respectively. p53 expression correlated positively with Ki-67 and World Health Organization (WHO) grade (r = 0.31 and r = 0.4, respectively). PR positivity correlated inversely with S100, p53, Ki-67, and WHO grade (r = -0.19, r = -0.14, r = -0.15, and r = -0.16, respectively). All secretory meningiomas were positive for EMA and PR and negative for S100, and this pattern exhibited a rostrocaudal gradient. The overall proportion of EMAPRS100 cases was significantly lower in the cranial vault (30.3%) than in the skull base (45.89%; P = 0.021). The proportion of WHO grade II-III tumors was greater in cranial vault than in skull base meningiomas.
Unsupervised methods detected an association between the anatomical location and tumor biology in meningiomas. Unlike the categorical associations that former studies had indicated, the present study revealed a rostrocaudal gradient in both the cranial vault and the skull base, correlating with human developmental biology.
脑膜瘤具有异质性,在解剖学、组织病理学和临床特征方面存在差异。脑膜瘤生物学的这种空间变异性被认为是由关键发育调节因子表达的差异所致。我们假设脑膜瘤生物学的变异性会遵循如胚胎学中的梯度变化,并对366例脑膜瘤患者进行了组织病理学和免疫组织化学梯度检测。
回顾性分析了2003年至2016年接受脑膜瘤治疗的366例患者的病历,包括年龄、性别、解剖定位、无复发生存期、总生存期、组织病理学诊断以及6种标志物的免疫组织化学结果:上皮膜抗原(EMA)、孕激素受体(PR)、CD34、S100、p53和Ki-67标记指数。
EMA、PR、S100、p53和CD34分别在94%、73%、49%、26%和23%的肿瘤中表达。p53表达与Ki-67和世界卫生组织(WHO)分级呈正相关(r分别为0.31和0.4)。PR阳性与S100、p53、Ki-67和WHO分级呈负相关(r分别为-0.19、-0.14、-0.15和-0.16)。所有分泌型脑膜瘤EMA和PR呈阳性,S100呈阴性,且这种模式呈现出从颅顶到颅底的梯度变化。颅顶EMAPRS100病例的总体比例(30.3%)显著低于颅底(45.89%;P = 0.021)。WHO II-III级肿瘤在颅顶脑膜瘤中的比例高于颅底脑膜瘤。
无监督方法检测到脑膜瘤的解剖位置与肿瘤生物学之间存在关联。与以往研究表明的分类关联不同,本研究揭示了颅顶和颅底均存在从颅顶到颅底的梯度变化,这与人类发育生物学相关。