HER-2在胃癌组织中的表达及其对预后的影响

发布时间：2018-12-12 15:26

【摘要】：背景:胃癌是危害人类健康的杀手之一,其发生发展涉及多种因素的改变,包括基因位点突变、等位基因缺失改变等,是多层次、多步骤、多阶段逐步演变的复杂过程。研究表明,原癌基因人类表皮生长因子受体2(HER-2)过表达及基因扩增与多种肿瘤的浸润、转移及预后密切相关。近年来,HER-2表达与胃癌发生发展关系的研究成为热点,然而国内外学者对HER-2基因在胃癌组织中表达情况的相关研究仍存在争议,没有把HER-2阳性胃癌分门别类进行大数据研究,也没有把HER-2检测作为胃癌患者的常规检查项目。目的:本研究初步探讨了HER-2基因过表达与胃癌生物学行为及病理特征的相关性,并回顾性对比分析其对患者生存期的影响,并分析HER-2能否作为胃癌预后的独立影响因素,从而为胃癌的个体化精准靶向治疗提供临床依据,并更好的预测胃癌患者的预后。方法:收集南阳市中心医院2012.01.01-2014.12.30经术后病理证实为胃癌且临床资料完整的组织标本84例,对病理组织标本采用免疫组织化学(IHC)及荧光原位杂交(FISH)检测HER-2的表达情况,并明确HER-2的表达与胃癌临床病理特征之间的关系及HER-2过表达对患者生存期及预后的影响,采用SPSS 21.0统计学软件对数据结果进行分析。结果:1.84例胃癌组织中HER-2阳性表达率约为11.9%(10/84);2.在男、女性胃癌患者中HER-2阳性表达率分别为13.33%、8.33%;在确诊年龄≤60岁及60岁的患者中阳性表达率分别为10.53%、13.04%;其中高、中分化25例样本中HER-2阳性表达率为8.00%(2/25),低分化组阳性表达率为13.56%(8/59);在胃癌切除标本最大长径≤5cm及最大长径5cm的组织标本中,HER-2阳性表达率分别为10.87%(5/46)、13.16%(5/38),以上各组临床病理特征间差异均无统计学意义(P0.05);3.在T1、T2期共计24例患者中,未发现HER-2阳性表达者,T3、T4期60例患者中HER-2阳性表达率为16.67%(10/60);在淋巴结转移阳性组及淋巴结转移阴性组其阳性表达率分别为18.00%(9/50)、2.94%(1/34);HER-2在肠型胃癌中阳性表达率明显高于在弥漫型胃癌中的阳性表达率(21.88%VS 5.77%);TNM分期为Ⅰ期的胃癌患者,未见HER-2阳性表达,Ⅱ期患者中,1例存在过表达,Ⅰ、Ⅱ期患者HER-2阳性表达率为3.03%(1/33),Ⅲ期患者HER-2阳性表达率为17.65%(9/51),以上各组间差异有统计学意义(P0.05);4.采用log-rank法进行预后的单因素生存分析,结果显示,存在HER-2过表达或基因扩增的胃癌患者,其中位生存时间明显短于HER-2阴性者(P0.05);5.采用Cox比例风险回归模型分析,结果表明,HER-2表达情况可以作为胃癌预后的独立参数。结论:1.在胃癌组织中存在HER-2过表达或基因扩增;2.在胃癌组织中,HER-2的表达与患者性别、确诊年龄、分化程度、肿瘤大小无明显相关性(P0.05);而与肿瘤组织浸润深度、有无淋巴结转移、胃癌TNM分期及胃癌Lauren分型密切相关(P0.05);3.存在HER-2过表达或基因扩增的胃癌患者,没有生存优势,预后较差,其中位生存时间明显短于HER-2阴性者;4.HER-2可以作为胃癌预后的独立影响因素。
[Abstract]:BACKGROUND: Gastric cancer is one of the killers of human health. The development of gastric cancer involves a variety of factors, including gene site mutation, allelic deletion, and so on. It is a complex process of multi-level, multi-step and multi-stage evolution. The study shows that the overexpression of the human epidermal growth factor receptor 2 (HER-2) and the gene amplification are closely related to the invasion, metastasis and prognosis of multiple tumors. In recent years, the research on the relationship between HER-2 expression and the development of gastric cancer has become a hot spot. HER-2 was not used as a routine test for gastric cancer patients. Objective: To study the relationship between the overexpression of HER-2 gene and the biological behavior and pathological characteristics of gastric cancer, and to analyze the effect of HER-2 on the survival of gastric cancer. thus providing a clinical basis for individualized and precise targeting treatment of the gastric cancer, and better predicting the prognosis of the gastric cancer patient. Methods: The expression of HER-2 was detected by immunohistochemistry (IHC) and in situ hybridization (FISH) in 84 patients with gastric cancer and complete clinical data. The relationship between the expression of HER-2 and the clinicopathological features of gastric cancer and the effect of HER-2 over-expression on the survival and prognosis of patients were determined. Results: The expression rate of HER-2 in 1. 84 gastric cancer tissues was about 11. 9% (10/ 84); 2. The positive expression rate of HER-2 in male and female patients with gastric cancer was 13.33% and 8.33%, respectively. The positive rate of expression of HER-2 was 10.53% and 13.04%, respectively. The positive expression rate of HER-2 was 8.00% (2/ 25) and 13.56% (8/ 59) in 25 samples with high and medium differentiation. The expression rate of HER-2 was 10.87% (5/ 46) and 13.16% (5/ 38), respectively. In the total of 24 patients in T1 and T2, the positive expression of HER-2 was 16.67% (10/ 60) in the patients with no HER-2 positive expression, T3 and T4. The positive expression of HER-2 was 18. 00% (9/ 50) and 2.94% (1/ 34), respectively. The positive rate of expression of HER-2 in the intestinal type of gastric cancer was higher than that in the case of gastric cancer (21. 88% VS 5.77%). The positive expression of HER-2 in gastric cancer with stage I was not found in the positive expression of HER-2. The expression rate of HER-2 in patients with stage 鈪，

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