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1、结直肠癌中Musashi-1、CD44v6与错配修复基因表达的研究结直肠癌中Musashi-1、CD44v6与错配修复基因表达的研究暨南大学硕士学位论文中文摘要目的检测结直肠癌和正常结直肠组织中干细胞标记物Musashi-1、CD44v6和错配修复基因hMSH2 hMLHI蛋白的表达，观察Musashi-1/CD44v6 双阳性细胞和hMSH2/ Musashi-1 双阳性细胞在结直肠癌和正常结直肠组织中的数量和分布特征 , 结合临床病理 特征分析各指标表达的关系 ;旨在探讨干细胞标记物和错配修复基因蛋白在结直肠癌中表 达的相关性 ,为进一步探索肿瘤干细胞与结直肠癌的分子病理学机制奠定基础。方
2、法采用免疫组化 SP 法检测结直肠癌和正常结直肠组织中错配修复基因hMSH、2 hMLH1和干细胞标记物 Musashi-1 、 CD44v6 蛋白的表达 ; 采用双重免疫组化SP-SAP 法检测Musashi-1 和 CD44v6 双阳性细胞和 hMSH2 和 Musashi-1 双阳性细胞的 数量及分布特征。结果1. 结直肠癌组织和正常结直肠组织中 hMSH2和(或)hMLH1蛋白表达缺失有 显著性差异(P0.05) ; hMSH2和(或)hMLHI蛋白表达缺失与肿瘤组织的分化程度 相关(P0.05),而与患者性别、年龄、浸润深度、肿瘤组织大小、 Dukes 分期以及淋巴转 移均无关 (P
3、0.05) 。2. 结直肠癌组织中 Musashi-1 和 CD44v6 的表达强度与阳性细胞表达的数 量都明显高于其在正常组织中的表达。正常结直肠组织中 Musashi-1 和 CD44v6 细胞沿 基底层腺体底部呈零散或单一细胞分布 , 结直肠癌组织中 Musashi-1 和 CD44v6 细胞沿基底 侧腺体呈散在或局灶性分布 ;Musashi-1 的表达与分化程度、淋巴结转移及 Dukes 分期有关 P0.05,CD44v6的表达与分化程度、肿瘤组织大小、浸润深度、淋巴结转移及 Dukes 分期 有关 (P0.05) ;Spearman等级相关分析显示：Musashi-1 与 CD44v
4、6表达呈正相关 (r1.000,P0.001) 。正常结直肠组织中 Musashi-1 与 CD44v6 双阳性细胞的数量约占 0.01-0.1%;而在结直肠癌组织中,Musashi-1与CD44v6双阳性细胞的数量约占肿瘤细胞的 2%-10%,它 们沿腺管样结构的基底呈局灶性或片状分布 ; 双阳性细胞的数量与结直肠癌的分化程度呈 负相关 , 分化程度越低, 双阳性细胞的数量则越多。 I结直肠癌中Musashi-1、CD44v6与错配修复基因表达的研究暨南大学硕士学 位论文3. 正常结直肠组织中Musashi-1与hMSH2双阳性细胞位于隐窝中下1/3腺 体的基底部呈零 散或单一细 胞分布;
5、在高 分化和部分中 分化结 直肠癌组织 中 见Musashi-1 与 hMSH2 双阳性细胞沿腺管样结构的基底呈散在或局灶性分布 ; 在低分化和部分中分化 腺癌组织中 ,hMSH2已经完全或大部分缺失。正常结直肠组织中Musashi-1与hMSH2双 阳性细胞的数量约占0.01-0.1%;高分化结直肠癌组织中,Musashi-1与hMSH2双阳性细 胞数占肿瘤细胞数低于 5%;在中分化腺癌中低于 2%,低分化癌中则未见双阳性表达细胞。Spearma n 等级相关分析显示:Musashi-1 与hMSH2表达呈负相关(r-1.000, P0.000)结论1. hMSH2和hMLHI与肿瘤的发生有
6、关；hMSH2和hMLHI缺失可能是肿瘤发 生的昀早期事件。2. Musashi-1 和 CD44v6 可作为结直肠肿瘤干细胞的特异性标记物 , 但Musashi-1 和CD44v6双阳性细胞是否均是肿瘤干细胞尚需体内外实验进一步证实。3. 在内外环境因素发生改变时 , 有可能首先导致成体干细胞的错配修复基因 突变而使其转变为肿瘤干细胞 , 昀终导致肿瘤的发生。关键词结直肠癌；错配修复基因(hMSH2 hMLHI);肿瘤干细胞；Musashi-1;CD44;免疫组化II结直肠癌中Musashi-1、CD44v6与错配修复基因表达的研究暨南大学硕士学 位论文 AbstractObjectives
7、To detect stem cell markers Musashi-1 、 CD44v6and the mismatch repair geneshMSH2and hMLH1protein expression in colorectal carcinoma and normal colorectal+ + +/ +tissues, the characteristics of Musashi-1 /CD44v6 and Musashi-1 hMSH2 cells incolorectal carcinoma and normal colorectal tissues are observ
8、ed; then combining theclinical and pathological features of each index and analysis the correlation of them. Inorder to investigate the relationship between stem cell markers and mismatch repairgenes in colorectal carcinoma. It can be a foundation for further study of tumor stemcells and colorectal
9、carcinoma molecular pathology mechanismMethodsImmunohistochemical SP and double immunohistochemical SP-SAP were used todetect the expression of mismatch repair gene hMSH2、 hMLH1 and stemcell markersMusashi-1 、 CD44v6 in colorectal carcinoma and normal colorectal tissues. To observethe characteristic
10、s of Musashi-1+/CD44v6+ cells and Musashi-1+/hMSH2+ cells incolorectal carcinoma and normal colorectal tissuesResults1. hMSH2 and hMLH1 protein expression deficiency has significant differencebetween in colorectal carcinoma tissues and normal colorectal tissues P0.05. Theexpression deficiency of hMS
11、H2 and hMLH1 protein relates with the differentiation ofcancer tissues P0.05. It has no relationship between the age and gender of patients 、infiltrationdepth 、lymph node metastasis and Dukes staging2. Theexpression of Musashi-1 and CD44v6 in colorectal carcinoma tissues isobviously higher than its
12、in normal tissues; Musashi-1 and CD44v6 cells are scattered inthe basement glands or focal distribution, the expression of Musashi-1 relates withdifferentiation、lymph node metastasis and Dukes staging P0.05;theexpression ofIII结直肠癌中Musashi-1、CD44v6与错配修复基因表达的研究暨南大学硕士学 位论文CD44v6relates with differentia
13、tion 、 infiltration depth 、 lymph node metastasis 、 size oftumor and Dukes staging P0.05;Spearman rank correlation analysis shows that thecorrelation between Musashi-1 and CD44v6 is positive in carcinoma tissues(r1.000,P0.001).The number of Musashi-1 and CD44v6 double positive cells about 2-10% inco
14、lorectal carcinoma tissues, but it is just 0.01-0.1% in normal colorectal tissues; theysettle along with glandular structures in the basement of focal or scattered. The numberof double positive cells is negative correction with the degree of differentiation, thelower the differentiation and the high
15、er strength and quantity3. Musashi-1 and hMSH2 double positive cells are scattered in the basement glandsor single cell distribution at basement of the foci in colorectal tissues; the numberof double positivecells is just 0.01-0.1% in normal colorectaltissues. Musashi-1 andhMSH2 double positive cells are scattered in the basement glands or focal distribution inhigh or middle differentiation of colorectal carcinoma tissues. The number of doublenormalofpositive cells is no more than 5% in high differentiation colorectal carcinoma tissuesand it is no more than 2%in middle differentia
