EGFR soluble isoforms and their transcripts are expressed in meningiomas.
EGFR soluble isoforms and their transcripts are expressed in meningiomas.
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DOI：
10.1371/journal.pone.0037204
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Labrousse F
中科院分区：
文献类型：
--
作者：
Guillaudeau A;Durand K;Bessette B;Chaunavel A;Pommepuy I;Projetti F;Robert S;Caire F;Rabinovitch-Chable H;Labrousse F
EGFR（表皮生长因子受体）参与许多肿瘤的发生。除了全长 EGFR（异构体 a）外，正常细胞和肿瘤细胞还产生缺乏胞内结构域的可溶性 EGFR 异构体 (sEGFR)。 sEGFR 同工型 b、c 和 d 由基因可变剪接产生的 EGFR 变体 2 (v2)、3 (v3) 和 4 (v4) mRNA 编码。因此，EGFR 蛋白表达分析的结果取决于抗体靶向的结构域。在脑膜瘤中，EGFR表达研究主要集中在EGFR亚型a。 sEGFR 和 EGFRvIII 突变体编码组成型活性截短受体，尚未进行研究。在 69 个脑膜瘤系列中，使用细胞外域靶向抗体 (ECD-Ab) 和细胞内域靶向抗体 (ICD-Ab) 通过免疫组织化学分析蛋白质表达。通过 RT-PCR 对 EGFRv1 至 v4 和 EGFRvIII mRNA 进行定量，并通过 MLPA 显示 EGFR 扩增。对临床数据、肿瘤切除（辛普森分级）、组织学类型、肿瘤分级和患者结果进行分析。ECD-Ab 的免疫化学染色比 ICD-Ab 更强。脑膜瘤表达 EGFRv1 至 -v4 mRNA，但不表达 EGFRvIII 突变体。中度或高 ECD-Ab 染色以及高 EGFRv1 至 v4 mRNA 水平与更好的无进展生存期 (PFS) 相关。当肿瘤切除评估为 Simpson 1 或 2 级、I 级与 II 级和 III 级脑膜瘤以及当 Ki67 标记指数低于 10% 时，女性的 PFS 也有所改善。我们的结果表明，除了整个亚型 a 之外，无 ICD 的 EGFR 蛋白亚型及其相应的 mRNA 变体也在脑膜瘤中表达。 EGFRvIII 没有表达。高表达水平似乎与更好的预后相关。这些结果表明，脑膜瘤中涉及 EGFR 通路的致癌机制可能与其他肿瘤类型不同。
The EGFR (epidermal growth factor receptor) is involved in the oncogenesis of many tumors. In addition to the full-length EGFR (isoform a), normal and tumor cells produce soluble EGFR isoforms (sEGFR) that lack the intracellular domain. sEGFR isoforms b, c and d are encoded by EGFR variants 2 (v2), 3 (v3) and 4 (v4) mRNA resulting from gene alternative splicing. Accordingly, the results of EGFR protein expression analysis depend on the domain targeted by the antibodies. In meningiomas, EGFR expression investigations mainly focused on EGFR isoform a. sEGFR and EGFRvIII mutant, that encodes a constitutively active truncated receptor, have not been studied. In a 69 meningiomas series, protein expression was analyzed by immunohistochemistry using extracellular domain targeted antibody (ECD-Ab) and intracellular domain targeted antibody (ICD-Ab). EGFRv1 to v4 and EGFRvIII mRNAs were quantified by RT-PCR and EGFR amplification revealed by MLPA. Results were analyzed with respect to clinical data, tumor resection (Simpson grade), histological type, tumor grade, and patient outcome.Immunochemical staining was stronger with ECD-Ab than with ICD-Ab. Meningiomas expressed EGFRv1 to -v4 mRNAs but not EGFRvIII mutant. Intermediate or high ECD-Ab staining and high EGFRv1 to v4 mRNA levels were associated to a better progression free survival (PFS). PFS was also improved in women, when tumor resection was evaluated as Simpson 1 or 2, in grade I vs. grade II and III meningiomas and when Ki67 labeling index was lower than 10%.Our results suggest that, EGFR protein isoforms without ICD and their corresponding mRNA variants are expressed in meningiomas in addition to the whole isoform a. EGFRvIII was not expressed. High expression levels seem to be related to a better prognosis. These results indicate that the oncogenetic mechanisms involving the EGFR pathway in meningiomas could be different from other tumor types.
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影响因子：
11.4
作者：
GREENFIELD, C;HILES, I;MCDONALD, N
通讯作者：
MCDONALD, N
影响因子：
4.1
作者：
Carroll, RS;Black, PM;Guha, A
通讯作者：
Guha, A
影响因子：
11.5
作者：
Halle, Cathinka;Lando, Malin;Lyng, Heidi
通讯作者：
Lyng, Heidi
影响因子：
12.7
作者：
Andersson, U;Guo, D;Henriksson, R
通讯作者：
Henriksson, R
DOI：
10.1007/978-0-387-98094-2_9
发表时间：
2009-01-01
期刊：
OVARIAN CANCER, SECOND EDITION
影响因子：
--
作者：
Baron, Andre T.;Lafky, Jacqueline M.;Maihle, Nita J.
通讯作者：
Maihle, Nita J.