【作者】 付利军；

【导师】 邱新光；

【作者基本信息】 郑州大学 ， 外科学， 2011， 硕士

【摘要】 研究背景甲状旁腺作为人体重要的内分泌腺体,其分泌的甲状旁腺激素(PTH)是人体内调节血钙水平的最重要激素。甲状旁腺肿瘤多数有典型的原发性甲状旁腺机能亢进症状,临床表现复杂,如表现为骨关节病变,泌尿系结石,或表现胃肠道症状,如恶心、反酸、食欲不振、消瘦等。本病临床较少见,且早期常缺乏典型的临床表现,往往造成误诊,延误治疗,造成严重后果,因此,早期诊断和早期治疗对甲状旁腺肿瘤有着重要意义。随着各种肿瘤分子致病机理研究的深入,甲状旁腺肿瘤的研究也有所进展。转化生长因子β1(Transfoming growth factor-β1,TGF-β1)是内源性细胞生长抑制因子,与肿瘤的关系较为复杂。TGF-β1能抑制早期肿瘤的发生,对中晚期肿瘤的发展、转移却又起促进作用。细胞周期蛋白D1(CyclinD1)是G1期细胞增殖信号的关键蛋白,是细胞周期的启动因子,其过表达可促进细胞从G1—S期的转化,从而使细胞过快生长,从而造成细胞恶性增殖。细胞周期蛋白与肿瘤的发生发展乃至预后都有密切的关系。为了进一步研究TGF-β1和CyclinD1在甲状旁腺肿瘤中的作用及相互关系,本实验拟用免疫组化的方法研究TGF-β1和CyclinD1在正常甲状旁腺组织、甲状旁腺腺瘤组织、甲状旁腺癌组织中的表达以及二者的关系。TGF-β1与CyclinD1的研究有助于我们了解甲状旁腺肿瘤的发生发展机制,为甲状旁腺肿瘤的临床诊断、治疗提供重要的理论依据。目的研究TGF-β1和CyclinD1在正常甲状旁腺组织、甲状旁腺腺瘤组织、甲状旁腺癌组织中的表达以及二者的关系；根据TGF-β1和CyclinD1在上述组织中表达及与病理类型的关系,研究二者在甲状旁腺肿瘤的发生过程中的作用。方法收集郑州大学第一附属医院甲状腺外科1997～2009年外科手术切除并经病理科医生诊断明确的甲状旁腺肿瘤组织标本共49例,其中甲状旁腺腺瘤组织43例,甲状旁腺癌组织6例,此外还包括10例正常甲状旁腺组织。通过SP免疫组化法检测了TGF-β1和CyclinD1的表达,并进行分组比较和统计学分析。结果10例正常组织中4例TGF-β1阳性,43例腺瘤组织中21例阳性,6例癌组织中4例阳性。10例正常组织中1例CyclinD1阳性,43例腺瘤组织中24例阳性,6例癌组织中5例阳性。TGF-β1蛋白的表达,甲状旁腺癌组织中TGF-β1阳性表达率高于甲状旁腺腺瘤组,甲状旁腺腺瘤组TGF-β1阳性表达率高于甲状旁腺正常组织,正常组、腺瘤组、癌组比较差异无统计学意义(P>0.05)；甲状旁腺癌组织中CyclinD1阳性表达率高于甲状旁腺腺瘤组,但差异无统计学意义(P>0.05)；甲状旁腺腺瘤组CyclinD1阳性表达率及甲状旁腺癌组织阳性表达率均高于甲状旁腺正常组织,差异有统计学意义(P<0.05),TGF-β1和CyclinD1在甲状旁腺腺瘤中的表达存在相关性(P<0.05)。结论CyclinD1的过度表达在甲状旁腺肿瘤发生中起重要作用,而TGF-β1则可能是参与了CyclinD1蛋白失活导致甲状旁腺肿瘤发生的关键环节。更多还原

【Abstract】 BackgroundParathyroid is the important endocrine gland in human, the secretion of parathyroid hormone (PTH) is the the most important hormones in human body which adjust blood calcium level. Parathyroid tumors most have the typical symptoms of primary hyperparathyroidism, the main clinical type is bone and bone-kidney mixed type, some of them show other symptoms, such as nausea, gastrointestinal symptoms, inappetence, emaciation, etc. It is often a lack of typical clinical manifestations in early stages.The main principle is detecting and treating in time.With the research of all kinds of tumor molecular pathogenesis,the research of parathyroid tumors also made some progress. Being a potent negative regulator of cell proliferation, transforming growth factor-β1(TGF-β1) plays an important role in inhibiting normal epithelial cell growth,and it has a complicated relationship with tumors. CyclinD1 is a key protein in G1 phage of the cell cycle. Its over expression can shorten the proeess from G1 to S phage, thus accelerate cell proliferation. In order to investigate the possible mechanism of parathyroid tumors and the clinicoPathologic significance of TGF-β1 and CyclinDl,the exression in parathyroid tumors, an Immunohistochemical SP method was used to examine the expression of the two kinds of proteins.ObjectiveTo investigate both the function of TGF-β1、CyclinD1 and the relationship between the two protein in parathyroid tumors and normal parathyroid tissues. It was helpful in learning the relationship between TGF-β1 signaling pathway and emergence development through study the TGF-β1 and CyclinD1 in parathyroid tumors. It also would provide the basis for diagnosis, judging to stage ofparathyroid tumors’ invasion and predicting the prognosis, finding new methods of therapy.MethodsTissues specimens were collected from the First Affiliated Hospital of Zhengzhou University from 1997 to 2009,10 cases of normal parathyroid tissues,43 cases of parathyroid adnoma tissues and 6 cases of parathyroid carcinoma tissues. SP Immunohistochemical technique was used to determine the expression of TGF-β1 and CyclinD1 in normal parathyroid tissues、parathyroid adenoma tissues and parathyroid carcinoma tissues. The data was analyzed by software SPSS 16.0.ResultsThere are 4 positive TGF-β1 expression (40%) and 1 overexpression of CyclinD1 (10%) in 10 normal parathyroid tissuess. There are 21 positive TGF-β1 expression (48.8%) and 24 overexpression of CyclinD1 (55.8%) in 43 parathyroid adenoma tissuess. There are 4 positive TGF-β1 expression (66.7%) and 5 overexpression of CyclinDl (83.3%) in 6 parathyroid carcinoma tissuess.The expression of TGF-β1 was not significantly different among the three groups.The expression of CyclinD1 protein was significantly different between normal parathyroid tissuess and parathyroid adnoma tissuess (P<0.05),and it was significantly different between normal parathyroid tissuess and parathyroid carcinoma tissuess(P<0.05),but it was not significantly different between parathyroid adnoma tissuess and parathyroid carcinoma tissuess (P>0.05). The expression of TGF-β1 was significantly related to the overexpression of CyclinD1 in the parathyroid adnoma tissuess, but it was not significantly related to the overexpression of CyclinD1 in the parathyroid carcinoma tissues. ConclusionsDerangements of the TGF-β1 pathyway due to CyclinD1 would be also implicated in the development of parathyroid tumors, the overexpression of CyclinD1 plays an important role in parathyroid tumors.更多还原