胃癌组织中人表皮生长因子受体2和瘦素的表达及意义

Expression of HER-2 and leptin in gastric cancer and their clinical significance

目的探讨胃癌组织中人表皮生长因子受体2（HER-2）、瘦素与瘦素受体的表达及其与临床病理特征和预后的关系，明确HER-2在胃癌原发灶与转移淋巴结的表达的一致性及胃癌组织中HER-2、瘦素和血管内皮生长因子（VEGF）表达水平的关系。方法选取110例胃癌手术切除组织和相应转移淋巴结作为研究对象，以96例正常胃黏膜组织作为对照，应用免疫组织化学法检测HER-2、瘦素、瘦素受体b亚型（OB．Rb）和VEGF蛋白的表达水平。结果HER-2、瘦素和OB—Rb在胃癌组织的表达阳性率分别为19．1％、49．1％和60．9％，显著高于正常胃黏膜组织（分别为8．0％、34．0％和46．0％，均P〈0．05）。HER-2在胃癌原发灶与淋巴结转移灶中的表达状态差异无统计学意义（P=0．607），一致性呈中等水平（Kappa=0．581）。在胃癌组织中，HER-2和瘦素的表达呈正相关（r=0．217，P=0．023），HER-2和瘦素与VEGF的表达也呈正相关（r=0．263，P=0．005；r=0．200，P=0．036）。HER-2和瘦素的表达与肿瘤浸润深度、淋巴结及远处转移、TNM分期等因素有关，而OB—Rb的表达与各临床病理学因素皆无关。Cox回归多因素分析结果显示，肿瘤低分化、体积大、转移淋巴结比例高、分期晚、术后不接受化疗和HER-2高表达为胃癌患者的独立不良预后因素。结论HER-2在胃癌原发灶与转移淋巴结中的表达状态基本一致。HER-2与瘦素在胃癌的侵袭进展、血管形成过程中可能起重要作用，HER-2高表达是胃癌患者的不良预后因素。

Objective To assess the expression of HER-2 and leptin in gastric cancer and evaluate their relationship with VEGF expression and clinicopathological features, and their prognostic value for gastric cancer patients. Methods One hundred and ten gastric cancer specimens and the corresponding metastatic lymph nodes were detected for HER-2 by immunohistochemistry （IHC）. All primary cancer tissues were detected for leptin, OB-Rb and VEGF. Ninty-six specimens of normal gastric mucosa served as the control. Results The expression level of HER-2, leptin and OB-Rb in gastric cancer tissues were significantly higher than those in normal tissues （19.1% vs. 8.0%, 49.1% vs. 34.0%, and 60.9% vs. 46.0% , P 〈 0.05 ）. HER-2 overexpression was moderately homogenous in primary gastric cancer and matastatic lymph nodes （P = 0. 607, Kappa = 0. 581 ）. There was a correlation between the expression of HER-2 and leptin, both of which were significantly correlated with tumor invasion depth, metastatic lymph nodes ratio （NR）, distal metastasis, TNM stage and VEGF expression. However, there was no significant correlation between OB-Rb expression and the clinicopathological features evaluated. Cox regression multivariate analysis showed that tumor size, histological grade, NR, stage, chemotherapy and HER-2 expression were independent prognostic factors. Conclusions HER-2 is stably expressed in primary gastric cancer and metastatic lymph nodes. HER-2 and leptin play an important role in the progression and angiogenesis of gastric cancer. High expression of HER-2 is a prognostic factor for poor outcome.