First Department of Pathology, Laiko Hospital, National and Kapodistrian University of Athens, Medical School, 75 Mikras Asias Street, Athens, Greece.
Virchows Arch. 2011 Jun;458(6):749-59. doi: 10.1007/s00428-011-1074-1. Epub 2011 Apr 15.
Although pERK and pAKT are reportedly activated in various neoplasms, little information is available about their significance in astrocytomas. Paraffin-embedded tissue from 82 patients with diffuse infiltrating astrocytomas (grades II to IV) was investigated for the association of pERK and pAKT activation with clinicopathological features, vascular endothelial growth factor (VEGF), isocitrate dehydrogenase 1 and microvascular parameters. Nuclear pERK labelling index (LI) increased with increasing cytoplasmic pERK LI and nuclear and cytoplasmic pAKT LI (p = 0.0019, p = 0.0260 and p = 0.0012, respectively). Accordingly, cytoplasmic pERK increased with increasing levels of nuclear (p = 0.0001) and marginally with cytoplasmic pAKT LI (p = 0.0526). Nuclear and cytoplasmic pERK LI and nuclear pAKT LI were positively correlated with tumour histological grade (p = 0.0040, p = 0.0238 for pERK and p = 0.0004 for pAKT, respectively). VEGF expression was correlated with nuclear pERK (p = 0.0099) and nuclear pAKT LI (p = 0.0002). Interestingly, pERK cytoplasmic LI increased with microvessel calibre (p = 0.0287), whereas pAKT nuclear LI was marginally related to microvessel density (p = 0.0685). The presence of IDH1-R132H was related only to histological grade and lower microvessel calibre. Multivariate survival analysis in the entire cohort selected cytoplasmic pAKT LI (p = 0.045), histological grade, microvessel calibre (p = 0.028), patients' age, gender and surgical excision as independent predictors of survival. Moreover, in glioblastomas, pERK nuclear LI emerged as a favourable prognosticator in the presence of IDH1-R132H. pERK and pAKT in astrocytomas are interrelated and associated with tumour grade and angiogenesis. Moreover, the importance of cytoplasmic pAKT immunoexpression in patients' prognosis and nuclear pERK immunoexpression in glioblastomas is confirmed.
尽管报道称 pERK 和 pAKT 在各种肿瘤中被激活，但关于它们在星形细胞瘤中的意义的信息却很少。研究了 82 例弥漫浸润性星形细胞瘤（II 级至 IV 级）患者的石蜡包埋组织，以探讨 pERK 和 pAKT 激活与临床病理特征、血管内皮生长因子（VEGF）、异柠檬酸脱氢酶 1 和微血管参数的关系。核 pERK 标记指数（LI）随细胞质 pERK LI 和核及细胞质 pAKT LI 的增加而增加（p=0.0019，p=0.0260，p=0.0012）。因此，细胞质 pERK 随核（p=0.0001）和细胞质 pAKT LI 的增加而增加（p=0.0526）。核和细胞质 pERK LI 与核和细胞质 pAKT LI 与肿瘤组织学分级呈正相关（p=0.0040，p=0.0238 用于 pERK，p=0.0004 用于 pAKT）。VEGF 表达与核 pERK（p=0.0099）和核 pAKT LI（p=0.0002）相关。有趣的是，细胞质 pERK LI 随微血管口径的增加而增加（p=0.0287），而核 pAKT LI 与微血管密度呈边缘相关（p=0.0685）。IDH1-R132H 的存在仅与组织学分级和较低的微血管口径相关。在整个队列中，多变量生存分析选择细胞质 pAKT LI（p=0.045）、组织学分级、微血管口径（p=0.028）、患者年龄、性别和手术切除作为生存的独立预测因子。此外，在胶质母细胞瘤中，IDH1-R132H 存在时，核 pERK LI 成为有利的预后预测因子。星形细胞瘤中的 pERK 和 pAKT 相互关联，并与肿瘤分级和血管生成有关。此外，还证实了细胞质 pAKT 免疫表达在患者预后中的重要性以及核 pERK 免疫表达在胶质母细胞瘤中的重要性。
