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c-Met表达在胶质母细胞瘤中的预后意义

Prognostic significance of c-Met expression in glioblastomas.

作者信息

Kong Doo-Sik, Song Sang-Yong, Kim Duk-Hwan, Joo Kyeung Min, Yoo Jin-San, Koh Jong Sung, Dong Seung Myung, Suh Yeon-Lim, Lee Jung-Il, Park Kwan, Kim Jong Hyun, Nam Do-Hyun

机构信息

Department of Neurosurgery, Samsung Medical Center and Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, Korea.

出版信息

Cancer. 2009 Jan 1;115(1):140-8. doi: 10.1002/cncr.23972.

Abstract

BACKGROUND

The authors investigated whether expression of c-Met protein in glioblastomas is associated with overall survival and biologic features representing tumor invasiveness in patients with glioblastomas.

METHODS

Paraffin-embedded specimens of glioblastomas from 62 patients treated in a single institution were assessed by immunohistochemical (IHC) analysis of c-Met expression. On the basis of the clinical data for these patients, the association between c-Met expression and clinicobiologic features representing tumor invasiveness was analyzed.

RESULTS

c-Met overexpression was detected in 29.0% (18 of 62) of glioblastomas. In patients with c-Met overexpression, the median survival was 11.7 months (95% confidence interval [95% CI], 9.9 months-13.5 months), compared with a median survival of 14.3 months (95% CI, 7.6 months-21.0 months) for patients whose tumors had no or little expression of c-Met (P=.031). On the radiographic analysis, 9 of 18 patients (50%) with tumors overexpressing c-Met demonstrated invasive and multifocal lesions on the initial magnetic resonance images, whereas only 9 of 44 patients (20.5%) with tumors that expressed no or little c-Met demonstrated these features (P=.030). Using immunohistochemistry, we also found a significant association between c-Met expression and matrix metalloproteinase-2,-9 (P=.020 and P=.013). Furthermore, Myc overexpression was found to be closely correlated with c-Met overexpression on IHC analysis (P=.004).

CONCLUSIONS

The authors suggest that c-Met overexpression is associated with shorter survival time and poor treatment response in glioblastomas, the mechanism for which is elevated tumor invasiveness on the molecular and clinical phenotypes. This implies that more effective therapeutic strategies targeting c-Met receptors may have important clinical implication.

摘要

背景

作者研究了胶质母细胞瘤中c-Met蛋白的表达是否与胶质母细胞瘤患者的总生存期以及代表肿瘤侵袭性的生物学特征相关。

方法

对在单一机构接受治疗的62例患者的胶质母细胞瘤石蜡包埋标本进行c-Met表达的免疫组织化学(IHC)分析。根据这些患者的临床数据,分析c-Met表达与代表肿瘤侵袭性的临床生物学特征之间的关联。

结果

在29.0%(62例中的18例)的胶质母细胞瘤中检测到c-Met过表达。在c-Met过表达的患者中,中位生存期为11.7个月(95%置信区间[95%CI],9.9个月至13.5个月),而肿瘤无c-Met表达或低表达的患者中位生存期为14.3个月(95%CI,7.6个月至21.0个月)(P=0.031)。影像学分析显示,18例c-Met过表达肿瘤患者中有9例(50%)在初始磁共振图像上表现为侵袭性和多灶性病变,而44例无或低表达c-Met肿瘤患者中只有9例(20.5%)表现出这些特征(P=0.030)。通过免疫组织化学,我们还发现c-Met表达与基质金属蛋白酶-2、-9之间存在显著关联(P=0.020和P=0.013)。此外,免疫组织化学分析发现Myc过表达与c-Met过表达密切相关(P=0.004)。

结论

作者认为,c-Met过表达与胶质母细胞瘤患者较短的生存时间和较差的治疗反应相关,其机制是在分子和临床表型上肿瘤侵袭性增强。这意味着针对c-Met受体的更有效治疗策略可能具有重要的临床意义。

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