【摘要】：背景:胃癌是危害人類健康的殺手之一,其發(fā)生發(fā)展涉及多種因素的改變,包括基因位點突變、等位基因缺失改變等,是多層次、多步驟、多階段逐步演變的復雜過程。研究表明,原癌基因人類表皮生長因子受體2(HER-2)過表達及基因擴增與多種腫瘤的浸潤、轉移及預后密切相關。近年來,HER-2表達與胃癌發(fā)生發(fā)展關系的研究成為熱點,然而國內外學者對HER-2基因在胃癌組織中表達情況的相關研究仍存在爭議,沒有把HER-2陽性胃癌分門別類進行大數(shù)據(jù)研究,也沒有把HER-2檢測作為胃癌患者的常規(guī)檢查項目。目的:本研究初步探討了HER-2基因過表達與胃癌生物學行為及病理特征的相關性,并回顧性對比分析其對患者生存期的影響,并分析HER-2能否作為胃癌預后的獨立影響因素,從而為胃癌的個體化精準靶向治療提供臨床依據(jù),并更好的預測胃癌患者的預后。方法:收集南陽市中心醫(yī)院2012.01.01-2014.12.30經(jīng)術后病理證實為胃癌且臨床資料完整的組織標本84例,對病理組織標本采用免疫組織化學(IHC)及熒光原位雜交(FISH)檢測HER-2的表達情況,并明確HER-2的表達與胃癌臨床病理特征之間的關系及HER-2過表達對患者生存期及預后的影響,采用SPSS 21.0統(tǒng)計學軟件對數(shù)據(jù)結果進行分析。結果:1.84例胃癌組織中HER-2陽性表達率約為11.9%(10/84);2.在男、女性胃癌患者中HER-2陽性表達率分別為13.33%、8.33%;在確診年齡≤60歲及60歲的患者中陽性表達率分別為10.53%、13.04%;其中高、中分化25例樣本中HER-2陽性表達率為8.00%(2/25),低分化組陽性表達率為13.56%(8/59);在胃癌切除標本最大長徑≤5cm及最大長徑5cm的組織標本中,HER-2陽性表達率分別為10.87%(5/46)、13.16%(5/38),以上各組臨床病理特征間差異均無統(tǒng)計學意義(P0.05);3.在T1、T2期共計24例患者中,未發(fā)現(xiàn)HER-2陽性表達者,T3、T4期60例患者中HER-2陽性表達率為16.67%(10/60);在淋巴結轉移陽性組及淋巴結轉移陰性組其陽性表達率分別為18.00%(9/50)、2.94%(1/34);HER-2在腸型胃癌中陽性表達率明顯高于在彌漫型胃癌中的陽性表達率(21.88%VS 5.77%);TNM分期為Ⅰ期的胃癌患者,未見HER-2陽性表達,Ⅱ期患者中,1例存在過表達,Ⅰ、Ⅱ期患者HER-2陽性表達率為3.03%(1/33),Ⅲ期患者HER-2陽性表達率為17.65%(9/51),以上各組間差異有統(tǒng)計學意義(P0.05);4.采用log-rank法進行預后的單因素生存分析,結果顯示,存在HER-2過表達或基因擴增的胃癌患者,其中位生存時間明顯短于HER-2陰性者(P0.05);5.采用Cox比例風險回歸模型分析,結果表明,HER-2表達情況可以作為胃癌預后的獨立參數(shù)。結論:1.在胃癌組織中存在HER-2過表達或基因擴增;2.在胃癌組織中,HER-2的表達與患者性別、確診年齡、分化程度、腫瘤大小無明顯相關性(P0.05);而與腫瘤組織浸潤深度、有無淋巴結轉移、胃癌TNM分期及胃癌Lauren分型密切相關(P0.05);3.存在HER-2過表達或基因擴增的胃癌患者,沒有生存優(yōu)勢,預后較差,其中位生存時間明顯短于HER-2陰性者;4.HER-2可以作為胃癌預后的獨立影響因素。
[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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