【作者】 闫亮；

【导师】 张云汉； 陈奎生；

【作者基本信息】 郑州大学 ， 病理学与病理生理学， 2004， 硕士

【摘要】 [背景和目的]：食管癌是我国常见的恶性肿瘤之一，严重威胁着人们的生命健康。食管癌的发生发展是一个多因素参与和多阶段演变的结果，其浸润、转移而导致的肿瘤扩散是引起病人死亡的重要因素。研究表明，肿瘤的浸润转移是由肿瘤细胞分泌的蛋白酶降解细胞外基质而启动。其中纤溶酶原被激活与肿瘤浸润转移的关系最为密切，另外，细胞粘附分子也起着重要作用。迄今为止，有关食管癌中uPA、P-选择素、p27活性的检测及其与临床病理因素关系的研究报道极少，uPA、P-选择素、nm23、p27在食管鳞癌浸润、转移中相互关系的相关报道更为罕见。探讨联合检测uPA、P-选择素、nm23、p27在食管癌浸润转移中的意义进而通过抑制uPA、P-选择素的活性和增加nm23、p27的活性为食管癌的靶向治疗提供理论依据。 [材料与方法]：收集河南省安阳市肿瘤医院2003年8-9月份手术切除标本54例，病理证实全部为鳞状细胞癌，其中Ⅰ级15例，Ⅱ级30例，Ⅲ级9例，发生淋巴结转移的有21例。每例均在癌灶、(?)癌旁(?)组织及远端正常粘膜处分别取材。运用原位杂交和免疫组织化学方法对54例食管鳞癌组织、22例癌旁不典型增生组织及54例正常粘膜中uPA和P-选择素的mRNA及蛋白的表达、nm23 mRNA的表达和p27蛋白的表达进行了系统检测及观察。统计学采用x~2检验对资料进行分析，以α=0.05为显著性检验水准。 [结果]郑州大学2(X)4硕士毕业论文食管鳞癌中uPA、P一选择素、nm23、p27的表达及其与浸润转移关系的研究1.54例食管鳞癌组织中uPA mRNA阳性表达主要位于细胞胞浆内，在组织学分级、大小、浸润深度和有无转移的不同组别间的表达其差异具有显著性(P<0.05);uPA蛋白阳性表达位于胞浆，其表达在不同浸润深度，有无转移的肿瘤之间有显著差异性(P<0.05)。2.食管鳞癌、癌旁不典型增生、正常食管粘膜组织中uPA mRNA阳性表达率分别是70.4%(38/54)、40.9%(9/22)、1 1.1%(6/54)，三组间两两比较差异均有显著，胜(P<0 .05)。3.食管鳞癌、癌旁不典型增生、正常食管粘膜组织中uPA蛋白阳性表达率分别是66.7%(36/54)、36.4%(8/22)、14.8%(8/54)，三组f’ed两两比较差异均有显著性 (P(0 .05)。4.54例食管鳞癌组织中P一选择素mRNA阳性表达主要位于细胞胞浆，其表达与组织学分级、浸润深度、淋巴结转移有关，差异具有显著性(P<0 .05);P一选择素蛋白的阳性表达位于细胞胞浆及胞膜上，其表达与浸润深度，淋巴结转移有关，差异具有显著性(P(0.05)。5.食管鳞癌、癌旁不典型增生、正常食管组织中P一选择素mRNA的阳性表达率分别为59.3%(32/54)、31.8%(7/22)、9.3%(5/54)，三组间两两比较差异均有显著性(P(0.05)。6.食管鳞癌、癌旁不典型增生、正常食管组织中P一选择素蛋白的阳性表达率分别为66.7%(36/54)、40.9%(9/22)、14.8%(8/54)，三组间两两比较差异均有显著性(P(0.05)。7.食管鳞癌、癌旁不典型增生、正常食管组织中nm23 mRNA的阳性表达率分别为35.2%(19/54)、63.6%(14/22)、85.2%(46/54)，三组间两两比较差异均有显著性(P<0 .05)。nm23 mRNA的表达位于细胞胞浆，其表达与浸润深度、淋巴结转移有关，差异具有显著性(P<0.05)。8.食管鳞癌、癌旁不典型增生、正常食管组织中p27蛋白的阳性表达率分别为31.5%(17/54)、59.1%(13/22)、81.5%(44/54)，三组间两两比较差异均有显著性 (P<0.05)。P27蛋白的表达位于细胞胞核内，胞浆和胞膜亦可见着色。其表达与浸润深度、淋巴结转移有关，具差异有显著性差异(P(0 .05)。9.uPA mRNA表达与蛋白表达之间差异无显著性(P>0 .05);P一选择素mRNA表达郑州大学2以孙硕士毕业论文食管鳞癌中uPA、P选择素、nm23、p27的表达及其与浸润转移关系的研究与蛋白表达之间有显著性差异(P<0.05)。10.uPA mRNA的表达与P一选择素mRNA的表达具有相关性(P<0.05);uPA蛋白的表达与P一选择素蛋白的表达无相关性(P> .05)。11.nm23 mRNA与uPA mRNA的表达和P一选择素mRNA的表达均具有相关性(P<0.05);与uPA蛋白的表达和P一选择素蛋白的表达均无相关性(P>.05)。12.p27蛋白的表达与uPA mRNA和蛋白的表达、P一选择素mRNA和蛋白的表达以及nm23 mRNA的表达之间均无相关性(P)0.05)。13.uPA、P一选择素、nm23和p27中2个或2个以上基因表达异常的病例与基因表达阴性或只有一个基因表达异常者相比，在癌浸润深度、淋巴结转移、肿瘤大小、大体类型、组织学分级方面差异显著(P<0 .05或P<0.01)。〔结论〕1.在食管鳞癌的发生过程中，uPA、P一选择素的活性在正常食管组织中呈现低表达，随着病变的加重，uPA及P一选择素活性依次显著增高，提示uPA及P一选择素参与了食管癌的发生、发展，uPA及P一选择素的激活是食管癌的早期事件。uPA及P一选择素有望成为食管癌的病情监测及早期诊断的生物学指标。2.nm23及p27的活性在正常食管组织呈现高表达，随着病变的加重，nm23及p27的活性显著降低，提示 nm23及p27参与了食管癌的发生发展，nm23及p27的失活是食管癌的早期事件。3.uPA mRNA的表达与食管鳞癌组织学分级、肿瘤大小、浸润深度和淋巴结转移有关;uPA蛋白的表更多还原

【Abstract】 [Background and objective]:The esophageal carcinoma is an one of the most familiar malignant tumor of our countries, it threatens seriously people life health. Cancerous occurrence in oesophagus development is tumor proliferation that the result that a many factors participates to turn into with many stages, its gradually, transfer but cause is an important factor to cause patient die. The research expresses that tumor start up invasion and metastasis because proteinase which is excreted by tumor cell separate Extracelluar Matrix. The connection of plasminogen’s activation and tumor’s invasion and metastasis is the most closely. Moreover, Cell adhesion molecules is also important to tumor’s invasion and metastasis. Up to the present, there are very few studies of the correlation of uPA,P-selectin,p27 to the characters of clinical pathology of esophageal carcinoma, the study of the correlation of uPA, P- selectin, nm23, p27 in the esophageal squamous cell carcinoma is even more few. It provide a theoretic foundation for that unite examine uPA, P- selectin, nm23, p27 to find the meaning in invasion and metastasis of esophageal squamous cell carcinoma, in addition, it also tell us that restrain activation of uPA or P- selectin and increase activation of nm23, p27 is likely to a new therapy method of esophageal carcinoma.[ Materials and methods]: 54 cases of esophageal carcinoma were collected in tumor hospital of Anyang City Henan province. All tissues were identified by pathologist, it is entirely squamous carcinoma. 15 cases are I rank,30 cases are II rank, 9 cases are III rank. 21 example appeared the lymph node metastasis, each all in the site of cancer, cancer beside and far normal mucoma cut a piece of tissue. In situ hybridization and immunohistochemistry was used to analyze the expression of uPA, P- selectin, nm23 and p27 in normal esophageal mucoma, esophageal squamous cell carcinoma and atypical hyperplasia. Data were performed with SPSS 10.0 software. Chi-square test was used and statistically significant level was considered as "alpha equals 0.05".[Results]1. The positive staining of uPA mRNA in 54 cases esophageal squamous cell carcinoma was located at cytoplasm of neoplasm, it’s expression had significant difference in histology classification, tumor size, invasion depth and lymph node metastasis group ( P<0.05 ) ; The positive staining of uPA protein in 54 cases esophageal squamous cell carcinoma was located at cytoplasm of neoplasm, it’s expression had significant difference in invasion depth and lymph node metastasis group ( P<0.05 ) .2. The rates of uPA mRNA positive expression in esophageal squamous cell carcinoma, atypical hyperplasia, normal esophageal mucoma were 70.4%(38/54), 40.9%(9/22), 11.1% (6/54) , each other compared in three group had all significant difference (P<0.05 ) .3. The rates of uPA protein positive expression in esophageal squamous cell carcinoma, atypical hyperplasia, normal esophageal mucoma were 66.7% (36/54), 36.4%(8/22), 14.8%(8/54) , each other compared in three group had all significant difference ( P<0.05 ) .4. The positive staining of P- selectin mRNA in 54 cases esophageal squamous cell carcinoma was located at cytoplasm of neoplasm, it’s expression had significant difference in histology classification, invasion depth and lymph node metastasis group(P<0.05) ; The positive staining of P- selectin protein in 54 cases esophagealsquamous cell carcinoma was located at cytoplasm and cytomembrane of neoplasm, it’s expression had significant difference in invasion depth and lymph node metastasis group ( P<0.05 ) .5. The rates of P- selectin mRNA positive expression in esophageal squamous cell carcinoma, atypical hyperplasia, normal esophageal mucoma were 59.3% (32/54)31.8% (7/22), 9.3% ( 5/54) , each other compared in three group had all significant difference ( P<0.05 ) .6. The rates of P- selectin protein positive expression in esophageal squamous cell carcinoma, atypical hyperplasia, normal esophageal mucoma were 66.7% (36/54). 40.9更多还原