Ki67、LRP在胃癌中的表达及其临床意义

发布时间：2018-08-06 10:57

【摘要】：目的:我国人口的恶性肿瘤发病人数逐年上升,居民的健康和生命受到严重威胁,胃癌是较为常见的恶性肿瘤,其发病率在男性各类肿瘤中居第2位,在女性居第3位。据流行病学预测,我国胃癌的发病率及死亡率在未来的20年均将呈现持续增长趋势。胃癌的发生、发展是多步骤、多环节、多基因参与并影响其发展及预后,由于缺乏便捷有效的普查手段,我国临床收治的胃癌大多数为进展期,对胃癌的早期诊断及有效治疗已成为当前一个亟待解决的问题。有效的化疗是延长胃癌患者生存期的重要方法之一,也是近几年研究的热点。Gerdes等学者于1983年首次制备出了Ki67抗体,Ki67位于细胞核内,与其他已知的蛋白均不具有明显的同源性,其与细胞的增殖活性有关。LRP是一种新的多药耐药相关蛋白,由Scheper等于1993年发现,起初是从一株人小细胞肺癌多耐药细胞中发现,该蛋白表现为对药物能量依赖性的蓄积能力下降。LRP存在于细胞质,是一种引起MDR的蛋白,其介导铂类、烷化剂等耐药[1],但LRP与胃癌预后报道很少。LRP与Ki67共同研究,分析二者的相关性及对胃癌的预后研究国内文献报道甚少。本实验采用免疫组化对胃癌组织、癌旁组织及正常胃粘膜组织进行SP法染色,分析Ki67、LRP的表达率及其与病例的年龄、性别、肿瘤浸润深度、分化程度、TNM分期、淋巴结转移等参数的相关性分析,从而为胃癌的预后判断及化疗提供可能性的理论依据。方法:随机选取40例胃癌患者及20例因胃部疾病就诊的非胃癌患者,实验标本为胃癌组织(40例)、相应癌旁5cm组织(40例)、正常胃粘膜组织(20例),采用免疫组织化学SP法检测标本中Ki67、LRP的表达率,并结合患者的性别、年龄、肿瘤浸润深度、分化程度、TNM分期行统计学分析,应用χ2检验对计数资料进行分析,研究胃癌中Ki67、LRP表达的相关性因素。P0.05时差异有统计学意义。结果:1 Ki67阳性表达为细胞核中可观察到淡黄色、棕黄色或棕褐色颗粒,本研究显示:Ki67在胃癌中的表达率为72.5%(29/40)、癌旁粘膜组织为45%(18/40)、正常胃粘膜组织中10%(2/20),组间的差异通过χ2检验相关性分析显示P0.05,具有统计学意义。2 LRP阳性表达为细胞质中可观察到淡黄色、棕黄色或棕褐色颗粒,本研究显示:LRP在胃癌的阳性表达率为75%(30/40)、癌旁粘膜组织52.5%(21/40)、正常胃粘膜组织25%(5/20),三组间的差异通过χ2检验相关性分析显示P0.05,具有统计学意义。3胃癌组织中Ki67和LRP的表达与临床病理因素的相关性分析3.1低分化胃癌组织中Ki67的表达率为85.19%(23/27),明显高于高中分化的表达率46.15%(6/13)(P0.05)。I+II期胃癌中Ki67的表达率为50.00%(6/12),明显低于III+IV期胃癌的表达率82.14%(23/28)(P0.05)。存在淋巴结转移的胃癌组织中Ki67的阳性表达率为82.14%(23/28),无淋巴结转移的表达率50.00%(6/12),两者之间差异具有统计学意义(P0.05)。Ki67的表达与患者的年龄、性别的差异无统计学意义(P0.05)。3.2 LRP蛋白在高中分化胃癌组织中的表达率为61.54%(8/13),明显低于低分化的表达率81.48%(22/27),但P0.05。LRP的表达在患者的年龄、性别、肿瘤分化程度、浸润深度、TNM分期、淋巴结转移参数的差异无统计学意义(P0.05)。4运用χ2检验相关分析,结果表明Ki67和LRP蛋白的表达无相关性(P0.05)。结论:1在胃癌中,Ki67呈高表达,与分化程度、浸润深度、TNM分期、淋巴结转移相关,与患者的年龄、性别无相关性。Ki67与肿瘤细胞的分化程度等生物学习性有关,可反映肿瘤的活性及进展状态。2在胃癌中,LRP呈高表达,与肿瘤浸润深度、分化程度、TNM分期、淋巴结转移以及患者的年龄、性别无相关性。但LRP在肿瘤细胞中表达高于正常胃组织,这提示胃癌的发生与LRP表达上调有关,可反映LRP对胃癌的原发性耐药性起重要作用。3在胃癌中,Ki67和LRP的表达无明显相关性,但两者可从肿瘤细胞的增殖、发展程度与原发耐药性方面综合评估肿瘤的发展,间接评估肿瘤预后,并为化疗用药提供指导方案。
[Abstract]:Objective: the number of malignant tumors in the population is rising year by year, and the health and life of the residents are seriously threatened. Gastric cancer is the most common malignant tumor. The incidence of the cancer is second in all kinds of male tumors and third in women. According to the epidemiological prediction, the incidence and mortality of gastric cancer in China will continue to continue in the next 20 years. The growth trend. The occurrence and development of gastric cancer is a multistep, multi link, multi gene participation and influence on its development and prognosis. Due to the lack of convenient and effective survey methods, most of the clinical gastric cancer in our country is progressing stage. Early diagnosis and effective treatment of gastric cancer have become an urgent problem to be solved. Effective chemotherapy is the prolongation of the stomach. One of the important methods of cancer patient's survival time is also a hot spot in recent years,.Gerdes and other scholars have prepared Ki67 antibody for the first time. Ki67 is in the nucleus and does not have obvious homology with other known proteins..LRP is a new multidrug resistance related protein related to cell proliferation activity, which is equal to 199 by Scheper. 3 years later, it was found that it was found in a human small cell lung cancer multidrug resistant cell, which showed that the accumulative capacity of the drug energy dependent decreased.LRP existed in the cytoplasm. It is a protein that causes MDR, which mediates the platinum, alkylating agents, and other drug resistant [1]. However, there are few reports of.LRP and Ki67 in the report of LRP and gastric cancer, and the analysis of the phase of the two. There are few domestic literature reports on the prognosis of gastric cancer. In this experiment, immunohistochemical method was used to stain gastric cancer tissue, para cancer tissue and normal gastric mucosa by SP staining. The expression rate of Ki67, LRP and the correlation analysis of age, sex, tumor invasion depth, differentiation range, TNM staging, lymph node metastasis were analyzed. The theoretical basis of the prognosis of gastric cancer and the possibility of chemotherapy was provided. Methods: 40 cases of gastric cancer and 20 non gastric cancer patients with gastric disease were randomly selected, the experimental specimens were gastric cancer tissue (40 cases), corresponding 5cm tissues (40 cases) and normal gastric mucosa (20 cases), and immunohistochemistry SP method was used to detect Ki67, LRP The rate of expression was combined with the sex, age, depth of invasion, degree of differentiation and TNM staging of the patients. The count data were analyzed by chi 2 test, and the correlation factor of Ki67 and LRP expression in gastric cancer was statistically significant. The results were that the positive expression of 1 Ki67 was that the nucleus could be observed to be yellowish and brown in the nucleus. The present study showed that the expression rate of Ki67 in gastric cancer was 72.5% (29/40), the mucosa adjacent to the carcinoma was 45% (18/40), and 10% (2/20) in the normal gastric mucosa. The difference between the groups showed P0.05 by the chi square 2 test correlation analysis, and the positive expression of.2 LRP could be observed in the cytoplasm of the pale yellow, brown, or brownish brown. The positive rate of LRP in gastric cancer was 75% (30/40), 52.5% (21/40) and 25% (5/20) in normal gastric mucosa, and the difference between three groups showed P0.05 by chi 2 test correlation analysis. The correlation between the expression of Ki67 and LRP in gastric cancer tissues and the correlation analysis of clinicopathological factors was 3.1 low scores. The expression rate of Ki67 in gastric carcinoma was 85.19% (23/27), which was significantly higher than the expression rate of high school differentiation 46.15% (6/13) (6/13). The expression rate of Ki67 was 50% (6/12) in.I+II stage gastric cancer, and was significantly lower than that of III+IV stage gastric carcinoma (23/28) (23/28) (P0.05). The positive expression rate of Ki67 in gastric carcinoma with lymph node metastasis was 82.14% (23/28). The expression rate of the metastasis was 50% (6/12). The difference was statistically significant (P0.05).Ki67 expression and the age of the patients. There was no significant difference in sex (P0.05) the expression rate of.3.2 LRP protein in high school differentiated gastric carcinoma was 61.54% (8/13), and the expression rate was lower than that of low differentiation 81.48% (22/27), but the expression of P0.05.LRP was in the expression of 81.48% (22/27). The age, sex, tumor differentiation, depth of invasion, depth of infiltration, TNM staging, and lymph node metastasis were not statistically significant (P0.05).4 using chi 2 test correlation analysis, the results showed that the expression of Ki67 and LRP protein was not correlated (P0.05). Conclusion: the expression of Ki67 in gastric cancer is high, with the degree of differentiation, depth of infiltration, TNM staging, lymph node metastasis. Correlation, related to the age, sex independent.Ki67 of the patient and the degree of differentiation of tumor cells, which can reflect the activity and progression of the tumor, and the progression state of.2 is highly expressed in gastric cancer, with the depth of the tumor, the degree of differentiation, the TNM staging, the lymph node metastasis and the age and sex of the patient, but LRP is in the tumor cells. The expression is higher than normal gastric tissue, which suggests that the occurrence of gastric cancer is related to the up regulation of LRP expression, which can reflect the important role of LRP in the primary drug resistance of gastric cancer,.3 in gastric cancer, there is no significant correlation between the expression of Ki67 and LRP, but both can evaluate the development of tumor from the proliferation of tumor cells, the degree of development and the primary drug resistance, and indirectly evaluate the development of the tumor. To estimate tumor prognosis and provide guidance for chemotherapy.
【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R735.2

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