【作者】 张颖；

【导师】 梁建芳；

【作者基本信息】 山西医科大学 ， 病理学与病理生理学， 2013， 硕士

【摘要】 背景及目的：子宫内膜腺癌是女性患恶性肿瘤常见疾病之一，其中最常见是子宫内膜样腺癌（endometrioid adenocarcinoma，EA），约占子宫内膜癌的60％，75％病例发生在绝经以后，只有5％病例发生在40岁以下的妇女，主要见于50－70岁的妇女。近年来由于人们生活水平、质量的提高，其患病率明显呈上升趋势，而且逐渐年轻化。从分子生物学水平检测分子靶向治疗药物的有效靶点是目前研究的热点，其中阻断与肿瘤发生密切相关的信号传导通路及关键作用的靶分子成为子宫内膜癌检测及治疗的重要依据。近些年许多学者研究发现，SPARC（Secreted Protein，Acidic and Rich in Cysteine）富含半胱氨酸的酸性蛋白与肿瘤发生的临床病理因素有密切关系。本课题主要研究SPARC蛋白及其mRNA与VEGF（血管生成因子）在子宫内膜样腺癌组织中的表达，以及两者之间的关系，最后证明两者之间在子宫内膜样腺癌临床病理学表达意义，希望在今后分子靶向治疗子宫内膜癌疾病中提供相关可靠的信息。对象和方法：对象：选择2005年1月－－2011年6月山西医科大学第一医院134例子宫内膜样腺癌的手术标本，所有病例术前均未行放、化疗。对照组是20例正常的子宫内膜组织，肿瘤组织和正常组织均经病理证实。方法：第一部分：运用免疫组化法检测134例子宫内膜样腺癌组织及20例正常子宫内膜组织中SPARC、VEGF的表达情况，来反映肿瘤组织内血管的生成潜能。第二部分：运用原位分子杂交技术检测134例子宫内膜样腺癌中SPARCmRNA的表达。统计学分析采用SPSS13.0进行数据处理。研究结果：（1）.SPARC在癌细胞中的表达与正常上皮细胞比较差异有显著性意义（P﹤0.05）,SPARC蛋白在正常子宫内膜组织和子宫内膜样腺癌中阳性率分别是95.0%和39.6%；VEGF在子宫内膜样腺癌中阳性率为67.2%，正常子宫内膜组织中阳性率为10.0%，二者比较差别有显著性意义。（2）SPARC在子宫内膜样腺癌细胞中的表达与临床病理特征有显著性差别（P﹤0.05），而与病人年龄无显著性差异（P＞0.05）；肿瘤组织中VEGF表达与浸润深度、组织学分级有显著性差异（P﹤0.05），而与年龄、手术分期、淋巴结转移无关（P﹥0.05）（3）SPARCmRNA的表达在子宫内膜样腺癌中低于正常子宫内膜组织，与临床病理因素之间的表达存在显著性差异（P﹤0.05）；SPARC与SPARCmRNA在子宫内膜样腺癌组织有明显差异，呈显著正相关（r=0.487，P=0.036）。（4）SPARC蛋白与VEGF蛋白之间的表达关系，在子宫内膜样腺癌中有明显差异，而且呈显著负相关（r=-0.213，P=0.001）（5）在子宫内膜样腺癌中，SPARC的表达高分化腺癌高于中分化和低分化腺癌（P<0.05）研究结论：SPARC及其mRNA在子宫内膜样腺癌中低分化表达或缺失与肿瘤的分化程度及淋巴结转移密切相关，是子宫内膜样腺癌预后不良的独立预后因子。SPARC蛋白和VEGF蛋白表达水平在子宫内膜样腺癌组织中呈显著负相关,考虑SPARC蛋白可能有抑制血管生成的条件，故此认为SPARC和VEGF蛋白之间相互抑制是治疗肿瘤疾病的新突破，对子宫内膜样腺癌的治疗有重要的科学依据。更多还原

【Abstract】 Background and objective: Endometrial adenocarcinoma is one of the women withcommon malignant tumors，is one of the most common endometrial adenocarcinoma,Accounts for about60%of endometrial cancers,75%cases have occurred after themenopause, Only5%of cases occur in women under the age of40, Mainly in50-70-year-old woman.In recent years, this trend has been increasing year by year. In orderto improve the quality of survival, from the level of molecular biology evaluation totesting the prognosis of patients, using effective drug appears especially important.Moreover, one block and tumor genesis are closely related to signaling pathways andare the key role in molecules endometrial cancer detection and treatment. And thesignal pathway and target molecules and whether endometrial cancer happens isclosely related to the exact molecular target therapy foundation. Recent studies havefound that rich in homocysteine acid Protein SPARC (Secreted Protein, Acidic andRich in Cysteine) and malignant tumor invasion and metastasis are closed related.This study investigates the SPARC and SPARCmRNA in adenocarcinoma ofendometrium tissues and angiogenesis factors in VEGF, hoping it can reachendometrial carcinoma molecular target therapy and provide a theoretical basis.Patients and methods: Patients:selected from January2005to June,2011in shanximedical university hospital, we take the first134adenocarcinoma of endometriumsurgical specimens both not put, chemotherapy history. The control group is20casesof normal endometrial organization, tumor tissue and normal tissue are confirmed bypathology. The first part:Application immunohistochemistry(IHC) method detected134examples within the film the cancerous tissue and20cases of normal endometrial organization the expression of SPARC. The expression of VEGF tumor tissuereaction in the formation of blood vessels is potential. The second part:Insituhybridization(ISH) for SPARCmRNA was examiner in134cases of endometrioidadenocarcinoma and20cases of normal endometrial organization The statisticalanalysis with SPSS13,.0carries on the data processing.Results:(1). The expression in cancer cells SPARC normal epithelial cells were moresignificant difference (P﹤0.05), SPARC in endometrioid adenocarcinoma were in for39.6%，SPARC in normal endometrial organization were in for95.0%；VEGF inendometrioid adenocarcinoma were in for67.2%, normal endometrial tissue positiverate10.0%, both the difference are significant.(2) SPARC endometrioid adenocarcinoma cells in the expression and tumor aredifferent. lymph node metastasis was significant difference between each (P﹤0.05),and differentiation have show significant correlation (P﹤0.05)and patient age(P>0.05); Tumor tissue VEGF expression in Infiltration depth and histological grading ofsignificant difference(P﹤0.05)，in age、operation stages、lymph node metastasis hasnothing to do(P﹤0.05)(3) The expression in cancer cells SPARCmRNA normal epithelial cells were moresignificant difference (P﹤0.05)，and clinical and pathological features were moresignificant differerce(P﹤0.05)； endometrioid adenocarcinoma tissue SPARCexpression and express a significant correlation between SPAECmRNA(r=0.487，P=0.036)(4) Endometrioid adenocarcinoma tissue SPARC expression and express a significantcorrelation between VEGF (r=-0.213，P＝0.001) (5)In the endometrioid adenocarcinoma, well-differentiated adenocarcinomas SPARCexpression was significantly higher than the differentiation in the cancer and lowdifferentiated in carcinoma (P <0.05)Conclusion: SPARC and SPARCmRNA in endometrioid adenocarcinoma lack andtumor differentiation and lymph node metastasis are closely related and theendometrioid adenocarcinoma prognosis independent prognostic factors. SPARCexpression and VEGF angiogenesis factor had significant correlation may be involvedin angiogenesis role. This molecular regulation mechanism may be a new way tocancer therapy, which became a meaningful reference to endometrial carcinomamolecular target therapy.更多还原