进展期胃癌人表皮生长因子受体2蛋白表达与临床病理学特征的关系

doi:10.16150/j.1671-2870.2017.02.009

摘要/Abstract

摘要： 目的评估人表皮生长因子受体2(human epidermal growth factor receptor-2, HER2)蛋白在胃癌中的表达情况,并分析其与胃癌患者临床病理学特征间的关系。方法收集2011年至2015年在瑞金医院行手术切除的胃癌患者的组织标本,检测其中HER2蛋白的表达情况,并分析患者的临床病理学特征与其HER2蛋白表达间的关系。结果 142例胃癌患者的病理组织中HER2蛋白表达呈阳性[免疫组织化学（immunohis tochemistry,IHC）3+],且HER2蛋白阳性表达与其局部浸润深度（P=0.002）、淋巴结转移（P<0.001）及TNM分期（P=0.030）相关。根据Lauren's 分型,肠型胃癌（30.5%）中的HER2蛋白阳性表达率高于弥漫型胃癌（16.1%,P<0.05）;而根据WHO分类标准,高-中分化胃癌（43.0%）中的HER2蛋白阳性表达率高于低-未分化胃癌（22.8%,P<0.05）。结论建立标准化的胃癌HER2蛋白免疫组织化学染色评分体系标准,对于筛选适合使用曲妥珠单抗治疗的患者显得尤为重要。肠型胃癌、高-中分化、TNM分期晚的胃癌患者的HER2蛋白阳性率明显高于其他胃癌患者,而这一部分患者可能从曲妥珠单抗靶向治疗中获益。

关键词: 人表皮生长因子受体2, 胃癌, 临床病理学特征, 免疫组织化学染色

Abstract: Objective: To investigate the expression of human epidermal growth factor receptor-2 (HER2) in advanced gastric cancer and the correlation between HER2 expression and clinicopathological features. Methods: A total of 542 consecutive patients with gastric cancer from 2011 to 2015 were enrolled, and all the patients received resection of the tumor at Ruijin Hospital. HER2 expression in tumor tissue was detected by immunohistochemistry in accordance with the Hoffmann scoring system. Correlation between HER2 expression and clinicopathological features was statistically analyzed. Results: One hundred and forty-one cases (26%) were scored as strongly positive for HER2 membrane staining (3+). HER2 positivity was statistically associated with local invasion (P=0.002), lymph node metastasis (P< 0.001), and TNM staging (P=0.030), respectively. HER2 overexpression was more frequently detected in intestinal (30.5%) than that in diffuse (16.1%) type of tumor according to Lauren's classification. Similarly, HER2 overexpression was more frequently detected in well or moderate differentiated (43.0%) than in poor or undifferentiated (22.8%) tumor according to WHO classification. Conclusions: An accurate standardized scoring system for HER2 expression in gastric cancer patients is important for selecting patients for trastuzumab treatment. This study indicates that patients with intestinal type, well differen-tiated and late staging hare a high rate of HER2 expression, and they were the candidates for targeted therapy using trastuzumab.

Key words: Human epidermal growth factor receptor-2, Gastric cancer, Clinicopathological characteristics, Immunohistochemistry

中图分类号:

R735.2

乔长婷, 李蕾, 邬安妮, 袁菲. 进展期胃癌人表皮生长因子受体2蛋白表达与临床病理学特征的关系[J]. 诊断学理论与实践, 2017, 16(02): 166-170.

QIAO Changting, LI Lei, WU Anni, YUAN Fei. Relationship between HER2 expression and clinicopathological features in advanced gastric cancer[J]. Journal of Diagnostics Concepts & Practice, 2017, 16(02): 166-170.

参考文献

[1] Torre LA, Bray F, Siegel RL, et al.Global cancer statistics, 2012[J]. CA Cancer J Clin,2015,65(2):87-108.
[2] Zhao P, Dai M, Chen W, et al.Cancer trends in China[J]. Jpn J Clin Oncol,2010,40(4):281-285.
[3] Wagner AD, Grothe W, Haerting J, et al.Chemotherapy in advanced gastric cancer: a systematic review and meta-analysis based on aggregate data[J]. J Clin Oncol,2006,24(18):2903-2909.
[4] Bang YJ, Van Cutsem E, Feyereislova A, et al.Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial[J]. Lancet,2010,376(9742):687-697.
[5] Tai W, Mahato R, Cheng K.The role of HER2 in cancer therapy and targeted drug delivery[J]. J Control Release,2010,146(3):264-275.
[6] Kaur A, Dasanu CA.Targeting the HER2 pathway for the therapy of lower esophageal and gastric adenocarcinoma[J]. Expert Opin Pharmacother,2011,12(16):2493-2503.
[7] Lambein K, Praet M, Forsyth R, et al.Relationship between pathological features, HER2 protein expression and HER2 and CEP17 copy number in breast cancer: bio-logical and methodological considerations[J]. J Clin Pathol,2011,64(3):200-207.
[8] Li Q, Wang D, Li J, et al.Clinicopathological and prognostic significance of HER-2/neu and VEGF expression in colon carcinomas[J]. BMC Cancer,2011,11:277.
[9] Yan B, Choo SN, Mulyadi P, et al.Dual-colour HER2/chromosome 17 chromogenic in situ hybridisation enables accurate assessment of HER2 genomic status in ovarian tumours[J]. J Clin Pathol,2011,64(12):1097-1101.
[10] Reichelt U, Duesedau P, Tsourlakis MCh, et al.Frequent homogeneous HER-2 amplification in primary and metastatic adenocarcinoma of the esophagus[J]. Mod Pathol,2007,20(1):120-129.
[11] Yan B, Yau EX, Choo SN, et al.Dual-colour HER2/chromosome 17 chromogenic in situ hybridisation assay enables accurate assessment of HER2 genomic status in gastric cancer and has potential utility in HER2 testing of biopsy samples[J]. J Clin Pathol,2011,64(10):880-883.
[12] Jørgensen JT, Hersom M.HER2 as a prognostic marker in gastric cancer-A cystematic analysis of data from the literature[J]. J Cancer,2012,3:137-144.
[13] Nagatsuma AK, Aizawa M, Kuwata T, et al. Expression profiles of HER2, EGFR, MET and FGFR2 in a large cohort of patients with gastric adenocarcinoma[J]. Gastric Cancer,2015 Apr,18(2):227-238.
[14] Carpenter G, Cohen S.Epidermal growth factor[J]. J Biol Chem,1990,265(14):7709-7712.
[15] Oda K, Matsuoka Y, Funahashi A, et al.A comprehensive pathway map of epidermal growth factor receptor signaling[J]. Mol Syst Biol,2005,1:2005.
[16] Normanno N, Bianco C, Strizzi L, et al. The ErbB receptors and their ligands in cancer: an overview[J]. Curr Drug Targets,2005 May,6(3):243-257.
[17] Baselga J, Swain SM. Novel anticancer targets: revisiting ERBB2 and discovering ERBB3[J]. Nat Rev Cancer,2009 Jul,9(7):463-475.
[18] Burstein HJ.The distinctive nature of HER2-positive breast cancers[J]. N Engl J Med,2005,353(16):1652-1654.
[19] Gschwind A, Fischer OM, Ullrich A.The discovery of receptor tyrosine kinases: targets for cancer therapy[J]. Nat Rev Cancer,2004,4(5):361-370.
[20] Toikkanen S, Helin H, Isola J, et al.Prognostic significance of HER-2 oncoprotein expression in breast cancer: a 30-year follow-up[J]. J Clin Oncol,1992,10(7):1044-1048.
[21] Park JS, Rha SY, Chung HC, et al.Clinicopathological features and prognostic significance of HER2 expression in gastric cancer[J]. Oncology. 2015;88(3):147-156.
[22] Grabsch H, Sivakumar S, Gray S, et al.HER2 expression in gastric cancer: Rare, heterogeneous and of no prognostic value - conclusions from 924 cases of two independent series[J]. Cell Oncol,2010,32(1-2):57-65.

编辑推荐 0

Metrics

阅读次数

全文

HTML			PDF

最新录用	在线预览	正式出版	最新录用	在线预览	正式出版
0	0	0	0	0	81

来源	本网站	其他网站

次数	39	42
比例	48%	52%

摘要

193

最新录用	在线预览	正式出版

0	0	193

来源	本网站	其他网站

次数	88	105
比例	46%	54%