The ErbB signalling pathway: protein expression and prognostic value in epithelial ovarian cancer.

The ErbB signalling pathway: protein expression and prognostic value in epithelial ovarian cancer.
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DOI:
10.1038/sj.bjc.6604471
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发表时间:
2008-07-22
影响因子:
8.8
通讯作者:
van der Zee, A. G. J.
van der Zee, A. G. J.
中科院分区:
医学1区
文献类型:
--
作者:
de Graeff, P.;Crijns, A. P. G.;ten Hoor, K. A.;Klip, H. G.;Hollema, H.;Oien, K.;Bartlett, J. M.;Wisman, G. B. A.;de Bock, G. H.;de Vries, E. G. E.;de Jong, S.;van der Zee, A. G. J.

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卵巢癌是西方世界妇科癌症最常见的死亡原因。目前的预后因素无法可靠预测个体卵巢癌患者对化疗的反应和生存。表皮生长因子受体 (EGFR) 和 HER-2/neu 在卵巢癌中频繁表达,但其预后价值仍不清楚。在本研究中,我们研究了 EGFR、EGFR 变异体 III (EGFRvIII)、HER-2/neu 和重要下游信号传导成分在大量上皮性卵巢癌患者中的表达和预后价值。使用组织微阵列平台对 232 个原发性肿瘤进行 EGFR、pEGFR、EGFRvIII、Her-2/neu、PTEN(10 号染色体上删除的磷酸酶和张力蛋白同源物)、总 AKT 和磷酸化 AKT (pAKT) 以及磷酸化 ERK (pERK) 的免疫组织化学染色,并与临床病理特征和生存相关。此外,通过 RT-PCR 测定了 45 个肿瘤中的 EGFRvIII 表达。我们的结果表明,阴性 PTEN 免疫染色与 I/II 期疾病 (P=0.006)、非浆液性肿瘤类型 (P=0.042) 相关,并且在多变量分析中与较长的无进展生存期 (P=0.015) 相关。 PTEN 染色阴性还可以预测 III 级或未分化浆液性癌患者无进展生存期的改善(P=0.011)。 pAKT 染色阳性与晚期疾病相关(P=0.006)。其他蛋白质仅以低水平表达,并且与任何临床病理学参数或生存无关。没有肿瘤呈 EGFRvIII 阳性。总之,我们的结果表明,PTEN 染色阴性的肿瘤可能代表具有相对良好预后的卵巢癌亚组。
Ovarian cancer is the most frequent cause of death from gynaecological cancer in the Western world. Current prognostic factors do not allow reliable prediction of response to chemotherapy and survival for individual ovarian cancer patients. Epidermal growth factor receptor (EGFR) and HER-2/neu are frequently expressed in ovarian cancer but their prognostic value remains unclear. In this study, we investigated the expression and prognostic value of EGFR, EGFR variant III (EGFRvIII), HER-2/neu and important downstream signalling components in a large series of epithelial ovarian cancer patients. Immunohistochemical staining of EGFR, pEGFR, EGFRvIII, Her-2/neu, PTEN (phosphatase and tensin homologue deleted on chromosome 10), total and phosphorylated AKT (pAKT) and phosphorylated ERK (pERK) was performed in 232 primary tumours using the tissue microarray platform and related to clinicopathological characteristics and survival. In addition, EGFRvIII expression was determined in 45 tumours by RT–PCR. Our results show that negative PTEN immunostaining was associated with stage I/II disease (P=0.006), non-serous tumour type (P=0.042) and in multivariate analysis with a longer progression-free survival (P=0.015). Negative PTEN staining also predicted improved progression-free survival in patients with grade III or undifferentiated serous carcinomas (P=0.011). Positive pAKT staining was associated with advanced-stage disease (P=0.006). Other proteins were expressed only at low levels, and were not associated with any clinicopathological parameter or survival. None of the tumours were positive for EGFRvIII. In conclusion, our results indicate that tumours showing negative PTEN staining could represent a subgroup of ovarian carcinomas with a relatively favourable prognosis.
在多中心研究中,影响卵巢癌p53表达的因素是临床结果的生物标志物。
DOI: 10.1038/sj.bjc.6603300
发表时间: 2006-09-04
影响因子: 8.8
作者:
de Graeff, P;Hall, J;Crijns, A P G;de Bock, G H;Paul, J;Oien, K A;ten Hoor, K A;de Jong, S;Hollema, H;Bartlett, J M S;Brown, R;van der Zee, A G J
通讯作者: van der Zee, A G J
DOI: 10.1016/s0002-9440(10)64681-0
发表时间: 2001-06-01
影响因子: 6
作者:
Kurose, K;Zhou, XP;Eng, C
通讯作者: Eng, C
DOI: 10.1002/ijc.20550
发表时间: 2005-01-01
影响因子: 6.4
作者:
Han, SW;Hwang, PG;Kim, NK
通讯作者: Kim, NK
DOI: 10.1017/s1462399404007781
发表时间: 2004-05-14
影响因子: 6.2
作者:
Hall, Jacqueline;Paul, Jim;Brown, Robert
通讯作者: Brown, Robert