【摘要】：目的:我國人口的惡性腫瘤發(fā)病人數(shù)逐年上升,居民的健康和生命受到嚴重威脅,胃癌是較為常見的惡性腫瘤,其發(fā)病率在男性各類腫瘤中居第2位,在女性居第3位。據(jù)流行病學預測,我國胃癌的發(fā)病率及死亡率在未來的20年均將呈現(xiàn)持續(xù)增長趨勢。胃癌的發(fā)生、發(fā)展是多步驟、多環(huán)節(jié)、多基因參與并影響其發(fā)展及預后,由于缺乏便捷有效的普查手段,我國臨床收治的胃癌大多數(shù)為進展期,對胃癌的早期診斷及有效治療已成為當前一個亟待解決的問題。有效的化療是延長胃癌患者生存期的重要方法之一,也是近幾年研究的熱點。Gerdes等學者于1983年首次制備出了Ki67抗體,Ki67位于細胞核內,與其他已知的蛋白均不具有明顯的同源性,其與細胞的增殖活性有關。LRP是一種新的多藥耐藥相關蛋白,由Scheper等于1993年發(fā)現(xiàn),起初是從一株人小細胞肺癌多耐藥細胞中發(fā)現(xiàn),該蛋白表現(xiàn)為對藥物能量依賴性的蓄積能力下降。LRP存在于細胞質,是一種引起MDR的蛋白,其介導鉑類、烷化劑等耐藥[1],但LRP與胃癌預后報道很少。LRP與Ki67共同研究,分析二者的相關性及對胃癌的預后研究國內文獻報道甚少。本實驗采用免疫組化對胃癌組織、癌旁組織及正常胃粘膜組織進行SP法染色,分析Ki67、LRP的表達率及其與病例的年齡、性別、腫瘤浸潤深度、分化程度、TNM分期、淋巴結轉移等參數(shù)的相關性分析,從而為胃癌的預后判斷及化療提供可能性的理論依據(jù)。方法:隨機選取40例胃癌患者及20例因胃部疾病就診的非胃癌患者,實驗標本為胃癌組織(40例)、相應癌旁5cm組織(40例)、正常胃粘膜組織(20例),采用免疫組織化學SP法檢測標本中Ki67、LRP的表達率,并結合患者的性別、年齡、腫瘤浸潤深度、分化程度、TNM分期行統(tǒng)計學分析,應用χ2檢驗對計數(shù)資料進行分析,研究胃癌中Ki67、LRP表達的相關性因素。P0.05時差異有統(tǒng)計學意義。結果:1 Ki67陽性表達為細胞核中可觀察到淡黃色、棕黃色或棕褐色顆粒,本研究顯示:Ki67在胃癌中的表達率為72.5%(29/40)、癌旁粘膜組織為45%(18/40)、正常胃粘膜組織中10%(2/20),組間的差異通過χ2檢驗相關性分析顯示P0.05,具有統(tǒng)計學意義。2 LRP陽性表達為細胞質中可觀察到淡黃色、棕黃色或棕褐色顆粒,本研究顯示:LRP在胃癌的陽性表達率為75%(30/40)、癌旁粘膜組織52.5%(21/40)、正常胃粘膜組織25%(5/20),三組間的差異通過χ2檢驗相關性分析顯示P0.05,具有統(tǒng)計學意義。3胃癌組織中Ki67和LRP的表達與臨床病理因素的相關性分析3.1低分化胃癌組織中Ki67的表達率為85.19%(23/27),明顯高于高中分化的表達率46.15%(6/13)(P0.05)。I+II期胃癌中Ki67的表達率為50.00%(6/12),明顯低于III+IV期胃癌的表達率82.14%(23/28)(P0.05)。存在淋巴結轉移的胃癌組織中Ki67的陽性表達率為82.14%(23/28),無淋巴結轉移的表達率50.00%(6/12),兩者之間差異具有統(tǒng)計學意義(P0.05)。Ki67的表達與患者的年齡、性別的差異無統(tǒng)計學意義(P0.05)。3.2 LRP蛋白在高中分化胃癌組織中的表達率為61.54%(8/13),明顯低于低分化的表達率81.48%(22/27),但P0.05。LRP的表達在患者的年齡、性別、腫瘤分化程度、浸潤深度、TNM分期、淋巴結轉移參數(shù)的差異無統(tǒng)計學意義(P0.05)。4運用χ2檢驗相關分析,結果表明Ki67和LRP蛋白的表達無相關性(P0.05)。結論:1在胃癌中,Ki67呈高表達,與分化程度、浸潤深度、TNM分期、淋巴結轉移相關,與患者的年齡、性別無相關性。Ki67與腫瘤細胞的分化程度等生物學習性有關,可反映腫瘤的活性及進展狀態(tài)。2在胃癌中,LRP呈高表達,與腫瘤浸潤深度、分化程度、TNM分期、淋巴結轉移以及患者的年齡、性別無相關性。但LRP在腫瘤細胞中表達高于正常胃組織,這提示胃癌的發(fā)生與LRP表達上調有關,可反映LRP對胃癌的原發(fā)性耐藥性起重要作用。3在胃癌中,Ki67和LRP的表達無明顯相關性,但兩者可從腫瘤細胞的增殖、發(fā)展程度與原發(fā)耐藥性方面綜合評估腫瘤的發(fā)展,間接評估腫瘤預后,并為化療用藥提供指導方案。
[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.
【學位授予單位】：河北醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2015
【分類號】：R735.2

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