【作者】 杨光；

【导师】 张祥宏；

【作者基本信息】 河北医科大学 ， 病理学与病理生理学， 2006， 博士

【摘要】 目的:近年来,乳腺癌的发病率逐年上升。钼靶X线摄影检查作为乳腺疾病诊断的首选方法,在乳腺癌的发现和诊断中发挥着重要作用,而其中微钙化征象在早期癌特别是乳腺导管内癌的筛查中更具有重要价值。资料显示,大约40%的乳腺癌在X线片中表现微钙化,90%的导管原位癌是通过钼靶X线微钙化被发现的。因此,结合钼靶X线片中微钙化征象,深入研究微钙化的形成机理、镜下病理特征表现及相关生物学特性,对加深X线片中微钙化征象的认识,提高乳腺癌的诊治水平以及通过影像学表现早期判断预后具有重要意义。传统认为乳腺癌微钙化的形成是一个被动、退化的过程,主要由癌组织坏死所致。最近研究显示某些异位钙化形成可能是一个主动的过程,很多与骨化相关的蛋白和细胞因子可能参与了钙化形成。骨桥蛋白(osteo- pontin,OPN)和骨连接蛋白(osteonectin,ON)均为骨基质磷酸化糖蛋白,与骨组织的矿化有关。研究表明,OPN和ON可能参与了心血管系统异位钙化及肾结石的形成。骨形态发生蛋白(bone morphogenetic prot- eins, BMPs)具有诱导骨形成的作用,其中BMP-2是最主要的骨生长调控因子。乳腺癌微钙化属于组织异位钙化,因此,乳腺癌细胞也可能具有与成骨细胞相似的生物学特性,通过相同的信号通路调控OPN、ON等骨基质蛋白的表达,进而影响局部钙盐的沉积。目前,有关钙相关蛋白与乳腺癌微钙化的关系及微钙化形成机制的研究国内外文献报道甚少。Bellahcene和Tokes等学者通过免疫组化和RT-PCR等技术初步检测了乳腺癌组织中OPN、ON的表达情况,推测OPN、ON的表达可能与乳腺癌微钙化形成有关。但是由于样本例数较少,且缺乏微钙化形成机理的研究。为了进一步深入探讨乳腺癌组织中微钙化的形成机制及临床意义,本研究依据钼靶X线片中微钙化表现分组,应用免疫组化、流式细胞技术和RT-PCR等方法检测人乳腺癌组织中OPN、ON和BMP-2的表达情况,分析其与微钙化和临床病理特征的关系;同时应用连续切片HE染色、钙盐特染及透射电镜观察分析了乳腺癌微钙化更多还原

【Abstract】 Objective: The past a few decases have witnessed an increasing in the incidence of breast carcinoma in our country. As the most useful screening method, mammography takes an important role in the detection and diagnosis of breast carcinoma. Among the different x-ray features, microcalcification signs on mammography are the most significant reference parameters in the screening and diagnosis of early carcinoma, especially intraductal breast carcinoma. Clinical data showed that microcalcification could be seen in approximately 40% of all breast carcinoma cases and 90% ductal carcinoma in situ cases were found bases on microcalcification signs in x-ray. Thus, it is very important to explore the relationship between X-ray microcalcification signs and pathological features and to elucidate the pathological bases, possible mechanism of formation of microcalcification in breast carcinoma.It is considered traditionally that the formation of breast microcalcifica- tion is a passive and degenerative process, caused by necrosis of cancer tissues. Recent researches demonstrated that the formation of some heterotopic calcification may be an initiative and regulated process, many calcium-related proteins and cell factors involved in the process. As bone matrix phosphorylation glycoproteins, osteopontin (OPN) and osteonectin (ON) take part in the mineralization of bone tissue. It was found that OPN and ON may also be involved in the formation of blood vascular calcification and kidney stone. Bone morphogenetic protein-2 (BMP-2), one of the important bone growth regulatory factors, is of great significance in the induction of osteoplast. Breast carcinoma microcalcification belongs to heterotopic calcification. Up to now, the following questions are still not clear: are the breast carcinoma cells siminlar biologically in some part to osteoblasts? What roles of OPN, ON and BMP-2 may take in deposition of calcium salt and the更多还原