Serum HER2 levels and HER2 status in tumor cells in advanced gastric cancer patients

Serum HER2 levels and HER2 status in tumor cells in advanced gastric cancer patients
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DOI:
10.1093/jjco/hyu174
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发表时间:
2015-01-01
影响因子:
2.4
通讯作者:
Ohtsu, Atsushi
Ohtsu, Atsushi
中科院分区:
医学4区
文献类型:
--
作者:
Sasaki, Takahide;Fuse, Nozomu;Ohtsu, Atsushi

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目的:转移性乳腺癌患者血清人表皮生长因子受体2水平升高,与肿瘤细胞中人表皮生长因子受体2过表达相关。然而,血清人表皮生长因子受体2在胃癌patients.Methods:我们回顾性分析了96例进展期胃癌患者的福尔马林固定石蜡包埋肿瘤组织和血清样本的患病率。采用免疫组织化学和荧光原位杂交技术检测肿瘤细胞中人表皮生长因子受体2的表达和基因扩增。血清人表皮生长因子受体2水平测定采用荧光免疫法。肿瘤细胞中人表皮生长因子受体2阳性定义为免疫组化2+荧光原位杂交阳性或免疫组化3+任何荧光原位杂交结果。19例患者(20%)肿瘤细胞中人表皮生长因子受体2阳性。血清人表皮生长因子受体2水平中位数为9.3ng/ml(范围,5.0- 332.4ng/ml),并且根据肿瘤细胞中人表皮生长因子受体2的状态,血清人表皮生长因子受体2水平显著分离(P < 0.0001,Wilcoxon秩和检验);人表皮生长因子受体2阴性和阳性患者的血清人表皮生长因子受体2水平中位数为8.9(范围,5.0-20.5)和24.0(范围,9.7-332.4)。有15名血清人表皮生长因子受体2阳性患者(16%)使用15 ng/ml的临界值。血清人表皮生长因子受体2的敏感性和特异性相对于人表皮生长因子受体2阳性的肿瘤细胞分别为53和94%,respectives.Conclusions:血清人表皮生长因子受体2的测量不能取代组织人表皮生长因子受体2的诊断在进展期胃癌患者。然而,血清人表皮生长因子受体2水平与肿瘤细胞中人表皮生长因子受体2过表达相关。进一步研究血清人表皮生长因子受体2作为预测指标和治疗监测指标的临床意义是必要的。
Objective: Increased serum human epidermal growth factor receptor 2 levels have been found in metastatic breast cancer patients and are correlated with human epidermal growth factor receptor 2 overexpression in tumor cells. However, the prevalence of serum human epidermal growth factor receptor 2 in gastric cancer patients has not been elucidated.Methods: We retrospectively analyzed formalin-fixed paraffin-embedded tumor tissues and serum samples from 96 advanced gastric cancer patients. Human epidermal growth factor receptor 2 expression and gene amplification in tumor cells were determined by immunohistochemistry and fluorescence in situ hybridization. Serum human epidermal growth factor receptor 2 levels were measured using a chemiluminescent immunoassay. Human epidermal growth factor receptor 2 positivity in tumor cells was defined as immunohistochemistry 2+ with fluorescence in situ hybridization positive or immunohistochemistry 3+ with any fluorescence in situ hybridization results.Results: All tissue samples and serum samples were successfully measured. Nineteen patients (20%) were human epidermal growth factor receptor 2-positive in tumor cells. The median serum human epidermal growth factor receptor 2 level was 9.3 ng/ml (range, 5.0-332.4 ng/ml), and serum human epidermal growth factor receptor 2 levels were significantly separated according to human epidermal growth factor receptor 2 status in tumor cells (P < 0.0001, Wilcoxon's rank sum test); median serum human epidermal growth factor receptor 2 levels in human epidermal growth factor receptor 2-negative patients and -positive patients were 8.9 (range, 5.0-20.5) and 24.0 (range, 9.7-332.4), respectively. There were 15 serum human epidermal growth factor receptor 2-positive patients (16%) using a cutoff value of 15 ng/ml. The sensitivity and the specificity of serum human epidermal growth factor receptor 2 with respect to human epidermal growth factor receptor 2 positivity in tumor cells were 53 and 94%, respectively.Conclusions: Serum human epidermal growth factor receptor 2 measurements cannot be substituted for tissue human epidermal growth factor receptor 2 diagnosis in advanced gastric cancer patients. However, serum human epidermal growth factor receptor 2 levels are associated with human epidermal growth factor receptor 2 overexpression in tumor cells. Further investigations of clinical significance of serum human epidermal growth factor receptor 2 as a predictive marker and a therapy-monitoring marker are warranted.