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背景与目的:分化障碍是肿瘤的一个重要生物学特性,但迄今为止,对肿瘤分化的研究远不如对肿瘤增殖的研究深入。本实验的目的是研究宫颈上皮癌变过程中细胞分化及其相关调节因素的改变。方法:实验分为宫颈正常鳞状上皮组(normal squamous epithelium,NSE)20例、非典型增生组(dysplasia squamous epithelial hyperplasia,DSEH)19例、原位癌组(squamou scarcinomainsitu,SCIS)39例和浸润癌组(invasivesquamousepithelialcarcinoma,ISEC)20例。用免疫组化SP法检测复层鳞状上皮细胞分化标记物Keratin(KT)10,14,19在各组组织的表达,并用免疫组化SP法及原位杂交分别检测!1整合素(!1-integrin)及!-连环素(!-catenin)的表达。结果:(1)KT10在正常宫颈组、非典型增生组、原位癌组和浸润癌组的强阳性率分别是85.0%、52.6%、18.0%和0%,呈逐渐降低趋势。原位癌组和浸润癌组明显低于正常组和非典型增生组(χ2=11.28,P<0.05;χ2=8.53,P<0.05)。(2)原位癌组和浸润癌组KT14和KT19二者均在部分病例中不表达;而在阳性表达的病例,其阳性细胞数明显多于正常组或非典型增生组,并且阳性表达细胞的空间位置上移,在原位癌病例常弥漫于上皮全层。(3)“1-integrin在正常组、非典型增生组、原位癌组和浸润癌组中的蛋白表达呈逐渐下降趋势,浸润癌组与正常组和非典型增生组两两比较有显著性差异(χ2=7.62,P<0.05,确切概率值0.014,P<0.05);”1-integrin在各组中的mRNA表达虽无显著性差异,但表达下降的趋势与其蛋白表达一致。(4)“-catenin在原位癌组和浸润癌组表达于细胞浆或核内,阳性病例表达细胞明显增多并上移。结论:在宫颈上皮癌变过程中,细胞终末分化受阻,”1-integrin和Wnt信号通路对上皮分化调节的紊乱,与上皮癌变过程中细胞分化的异常有关;原位癌细胞与浸润癌细胞在KT10和“1-integrin表达方面已无本质的区别。
BACKGROUND & OBJECTIVE: Differentiation disorders are an important biological feature of tumors, but so far the research on tumor differentiation has far less research on tumor proliferation. The purpose of this experiment is to study the changes of cell differentiation and related regulatory factors in the carcinogenesis of cervical epithelium. Methods: The experiment was divided into 20 cases of normal squamous epithelium (NSE), 19 cases of dysplasia squamous epithelial hyperplasia (DSEH), 39 cases of squamous scarcinoma (SCIS) 20 cases of infection group squamous cell carcinoma (ISEC). Immunohistochemical SP method was used to detect the expression of keratin (KT) 10, 14, 19 in the squamous cell of squamous epithelial cells. Immunohistochemical SP method and in situ hybridization were used to detect the expression of integrin 1-integrin and! -catenin expression. Results: (1) The positive rates of KT10 in normal cervical group, atypical hyperplasia group, in situ carcinoma group and invasive carcinoma group were 85.0%, 52.6%, 18.0% and 0%, respectively, showing a decreasing trend. In situ carcinoma and invasive carcinoma were significantly lower than those in normal and atypical hyperplasia (χ2 = 11.28, P <0.05; χ2 = 8.53, P <0.05). (2) Both KT14 and KT19 in in situ carcinoma and invasive carcinoma were not expressed in some cases; while in positive cases, the positive cells were significantly more than those in normal group or atypical hyperplasia group, and positive cells The spatial location of the shift in situ cancer cases often diffuse in the epithelial full-thickness. (3) The protein expression of 1-integrin in normal group, atypical hyperplasia group, in situ carcinoma group and invasive carcinoma group showed a decreasing trend, the invasive carcinoma group compared with normal group and atypical hyperplasia group had significant difference (Χ2 = 7.62, P <0.05, exact probability 0.014, P <0.05). Although there was no significant difference in mRNA expression of 1-integrin in each group, the trend of expression decline was consistent with its protein expression. (4) The expression of catenin in cytoplasm or nucleus of carcinoma in situ and invasive carcinoma group was significantly higher than that in the positive cases (P <0.05) .Conclusion: In the process of carcinogenesis of cervical epithelium, cell terminal differentiation is blocked, ”1-integrin and Wnt signaling pathways regulate epithelial differentiation disorders that are associated with abnormal cell differentiation during epithelial carcinogenesis; in situ cancer cells and invasive cancer cells have no essential differences in KT10 and 1-integrin expression.