Stem cell marker nestin and c-Jun NH2-terminal kinases in tumor and peritumor areas of glioblastoma multiforme:: Possible prognostic lmplications
Stem cell marker nestin and c-Jun NH2-terminal kinases in tumor and peritumor areas of glioblastoma multiforme:: Possible prognostic lmplications
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DOI：
10.1158/1078-0432.ccr-07-1229
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发表时间：
2007-12-01
影响因子：
11.5
通讯作者：
Sica, Gigliola
中科院分区：
文献类型：
--
作者：
Mangiola, Annunziato;Lama, Gina;Sica, Gigliola
目的：脑肿瘤起源于干细胞或短暂分裂前体转化的假说。此外，c-Jun nh2末端激酶（JNKs）也参与了胶质瘤的形成。本研究分析了干细胞标志物nestin和JNK在多形性胶质母细胞瘤（GBM）和肿瘤周围组织中的表达，并评估了它们可能的预后意义。实验设计：采用免疫组化方法检测20例GBMs中Nestin、总JNK （tJNK）和磷酸化JNK （pJNK）的表达。样本分别来自肿瘤（第一个区域）、距离< 1 cm的组织（第二个区域）和距离宏观肿瘤边界1 ~ 3.5 cm的组织（第三个区域）。分析患者年龄、Karnofsky性能状态、性别、蛋白表达与生存率的关系。结果：肿瘤内绝大多数细胞存在巢蛋白胞质免疫反应性，肿瘤周围细胞较少。tJNK在细胞核和细胞质中广泛表达；pJNK主要位于细胞核，在肿瘤和肿瘤周围组织的细胞中发现了不同比例的pJNK。Nestin和JNK在肿瘤周围的表达与肿瘤细胞的存在无关。单因素分析显示，第二区pJNK/nestin和(pJNK/ tJNK)/nestin比值分别为>= 2.6119和>= 0.026的患者生存时间更长（19个月vs 12个月，P = 0.01）。相同的变量在多变量分析中显示出独立的预后价值。结论：Nestin和JNK的表达表明，肿瘤周围组织，独立于肿瘤细胞的存在，可能呈现转化的迹象。此外，该组织中的pJNK/nestin和(pJNK/tJNK)/nestin比值似乎对GBM患者的预后有一定影响。
Purpose: It has been hypothesized that brain tumors are derived from stem cell or transiently dividing precursor transformation. Furthermore, c-Jun NH2-terminal kinases (JNKs) have been involved in gliomagenesis. This study analyzes stem cell marker nestin and JNK expression in glioblastoma multiforme (GBM) and peritumor tissue and assesses their possible prognostic implications.Experimental Design: Nestin and both total JNK (tJNK) and phosphorylated JNK (pJNK) expression was investigated by immunohistochemistry in 20 GBMs. Samples were derived from tumors (first area), from tissues at a distance < 1 cm (second area), and between 1 and 3.5 cm (third area) from the macroscopic tumor border. The relationships between patients' age, Karnofsky performance status, gender, protein expression, and survival were analyzed.Results: Nestin cytoplasmic immunoreactivity was observed in the majority of cells in tumor but infrequently in peritumor areas. tJNK, observed in the nucleus and cytoplasm, was widely expressed in the three areas; pJNK, mostly located in the nuclei, was found in a variable percentage of cells in the tumor and peritumor tissue. Nestin and JNK expression in peritumor areas was independent of the presence of neoplastic cells. Univariate analysis indicated that survival was longer (19 versus 12 months; P = 0.01) for patients whose pJNK/nestin and (pJNK/ tJNK)/nestin ratios in the second area were >= 2.6119 and >= 0.026, respectively. The same variables showed an independent prognostic value in multivariate analysis.Conclusions: Nestin and JNK expression indicates that peritumor tissue, independently of the presence of neoplastic cells, may present signs of transformation. Moreover, pJNK/nestin and (pJNK/tJNK)/nestin ratios in that tissue seem to have some prognostic implications in GBM patients.