共查询到19条相似文献,搜索用时 125 毫秒
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目的:分析胃癌组织微卫星不稳定性、hMLH1蛋白表达以及两者的关系。方法:选取65例胃癌组织标本,常规酚-氯仿法提取DNA,选取基因组上的五个微卫星位点BAT26、BAT25、D5S346、D2S123和D17S250,进行PCR扩增,扩增产物加入GeneScan 500size standard共同热变性后,用60g/L的SLPA添加8mol/L尿素做筛分递质的毛细管电泳进行分析。被检测的5个微卫星位点如出现≥2个位点的不稳定,定为微卫星的高度不稳定(MSI-H),1个位点出现不稳定定为微卫星的低度不稳定(MSI-L),没有位点出现不稳定定为微卫星稳定(MSS),石蜡切片常规免疫组织化学SP方法检测hMLH1蛋白的表达。结果65例胃癌组织中,有21例(32.3%)表现为MSI-H,20例(30.8%)有hMLH1蛋白表达的缺失。在21例MSI-H的胃癌组织中,18例(85.7%)有hMLH1蛋白表达的缺失。44例MSI-L/MSS的胃癌组织中仅2例(4.5%)有hMLH1表达的缺失。胃癌的MSI-H与hMLH1蛋白表达的缺失高度相关,P<0.01。其中,25例高分化腺癌有7例(28.0%)表现为MSI-H,6例(24.0%)有hMLH1表达的缺失;40例中低分化腺癌14例(35.0%)表现为MSI-H,12例(30.0%)有hMLH1蛋白表达的缺失。26例早期癌有1例(3.8%)表现为MSI-H,2例(7.7%)有hMLH1蛋白表达的缺失;39例中晚期癌20例(51.3%)表现为MSI-H,17例(43.6%)有hMLH1蛋白表达的缺失。微卫星不稳定在中晚期胃癌明显高于早期胃癌(P<0.01),但在不同分化程度的胃癌间差异无统计学意义;hMLH1蛋白表达缺失与分化程度无关,但在早期与中晚期的胃癌间差异有统计学意义,P<0.05。结论:由hMLH1基因所致细胞修复功能缺陷与部分胃癌的发生有关,而与胃癌的生物学行为无关;胃癌的微卫星不稳定性随着肿瘤的演进而增加。 相似文献
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目的 检测临床手术切除43例胃癌及相应正常组织COX-2、hMLH1和hMSH2微卫星不稳定状态MSI及三种基因启动子甲基化情况,并进一步探讨它们与胃癌发生的关系。方法 采用聚合酶链反应(PCR)技术检测5个位点的MSI状态;甲基化特异性PCR(Methylation specific PCR,MSP)方法检测胃癌及正常组织COX-2、hMLH1及hMSH2三种基因启动子CpG岛甲基化状态。结果 43例胃癌中MSI总检出率为48.84%(21/43),五个位点的MSI检出率无显著差别。COX-2和hMLH1基因启动子CpG岛甲基化在43例胃癌中分别有8例和13例,正常组织中未检测到。hMSH2基因启动子CpG岛在胃癌及正常组织中均未检测到甲基化。在MSI-H组hMLH1基因启动子CpG岛甲基化率显著高于MSS组(P〈0.01);而在MSI-H和MSI-L组间以及MSI-L和MSS无差别。MSI-H组中COX-2基因启动子CpG岛甲基化8例,且有7例胃癌同时出现hMLH1和COX-2基因启动子CpG岛甲基化。结论 在MSI胃癌(尤其是MSI-H型胃癌)的发生、发展过程中可能同时出现了hMLH1和COX-2基因启动子CpG岛的甲基化(即表型遗传修饰)。MSI胃癌hMLH1基因启动子CpG岛甲基化率高于MSS胃癌,提示检测hMLH1基因启动子CpG岛甲基化对于判断肿瘤类型有一定意义。 相似文献
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目的探讨幽门螺杆菌(Hp)对胃癌中hMLH1和hMSH2基因表达的影响和Hp的致癌机制.方法利用免疫组织化学S-P法检测胃癌、癌旁和胃炎黏膜中hMLH1、hMSH2 基因的表达情况.结果在全部被检组织中,Hp感染组hMLH1和hMSH2表达阳性率均低于相应的非感染组,其中胃癌组织中hMSH2表达阳性率在Hp感染组(54.7%)和非感染组(82.1%)差异有显著性(P<0.05).结论 Hp感染引起hMLH1和hMSH2基因表达降低,这可能是Hp导致胃癌的分子机制之一. 相似文献
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《中国肿瘤临床与康复》2019,(3)
目的探讨散发性微卫星不稳定性结直肠癌患者突变型P53基因(Mt-p53)、B淋巴细胞瘤-2基因(bcl-2)、人类错配修复基因1(hMLH1)和人类错配修复基因2(hMSH2)蛋白表达及临床意义。方法选取2017年10月至2018年11月间山东大学齐鲁医院收治的149例经手术切除的散发性结直肠癌(SRC)标本作为肠癌组,另收集距癌组织边缘10cm处的健康肠组织标本149例为健康组。采用PCR仪及遗传分析仪对肠癌组标本进行微卫星不稳定(MSI)检测,采用免疫组化检测试剂盒检测两组标本Mt-p53、bcl-2、hMLH1和hMSH2蛋白表达情况。结果 149例SRC标本中,位点D2S123 MSI阳性率为12. 1%,位点BAT26MSI阳性率为18. 1%,位点D17S261 MSI阳性率为10. 1%,位点D17S799 MSI阳性率为8. 1%。其中MSI-L为18例,MSI-H为22例,MSI总阳性率为26. 8%。149例肠癌组中Mt-p53蛋白表达阳性率为67. 1%(100例),bcl-2蛋白表达阳性率为77. 9%(116例),hMLH1蛋白表达阳性率为73. 2%(109例),hMSH2蛋白表达阳性率为71. 1%(106例)。149例健康组中Mt-p53、bcl-2、hMLH1和hMSH2蛋白表达阳性率均为100. 0%(149例)。两组标本各蛋白表达情况比较,差异均有统计学意义(均P <0. 01)。MSI阳性标本及阴性标本中Mt-p53、bcl-2和hMSH2蛋白表达阳性率比较,差异均无统计学意义(均P> 0. 05)。MSI阳性标本及阴性标本中hMLH1蛋白表达阳性率比较,差异有统计学意义(P <0. 05)。结论 SRC的发生不仅与Mt-p53的失活和bcl-2的激活有关,还与错配修复(MMR)基因突变引发的MSI相关,是SRC新的重要发生机制。MSI与Mt-p53、bcl-2和hMSH2蛋白表达情况相关性不大,但部分MSI与hMLH1蛋白表达显著相关,其余MSI可能涉及其他MMR基因。 相似文献
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[目的]分析散发性结直肠癌中的hMLH1和hMSH2蛋白表达情况。[方法]选取经病理学确诊并在术前未接受过放疗或化疗的结直肠癌手术切除标本127例,以及内镜活检无肿瘤患者肠黏膜上皮20例。用免疫组化方法检测hMLH1和hMSH2蛋白表达情况。[结果]结直肠癌组织中hMSH2蛋白表达缺失率为65.4%(83/127),高于对照肠组织(20.0%,4/20)(χ2=14.714,P〈0.001)。结直肠癌组织中hMSH2蛋白缺失率随T分期增加而增加(χ2=8.233,P=0.041);与N分期有关(χ2=20.235,P〈0.001),有淋巴结转移者患者中hMSH2蛋白表达缺失率达87.1%(27/31),高于无淋巴结转移患者(54.2%)(χ2=9.250,P=0.002)。hMLH1蛋白表达缺失率为74.0%,与T分期(χ2=29.115,P〈0.001)、N分期(χ2=9.807,P=0.006)、M分期(χ2=7.363,P=0.007)有关。[结论]结直肠癌组织中存在hMLH1和hMLH2蛋白表达缺失,通过免疫组化方法检测,可以简便、准确地发现错配修复基因的突变,可为后期的治疗和预后判断提供参考。 相似文献
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[目的]评价错配修复基因hMLH1和hMSH2在结直肠癌中的表达及意义.[方法]经病理学确诊的结直肠癌手术切除标本85例,术前均未接受过放疗或化疗,免疫组化检测hMLH1和hMSH2蛋白表达情况.[结果]85例结直肠癌组中,hMSH2缺失率为69.4%(59/85),hMLH1蛋白缺失率为78.8%(67/85).hMSH2蛋白缺失率在T1、T2、T3和T4期结直肠肿瘤中的缺失率分别为50.0%、43.8%、71.1%和82.8%,随T分期增加而增加(x2=11.037,P=0.012).有淋巴结转移者的hMSH2蛋白缺失率达88.57% (31/35),而无淋巴结转移患者的hMSH2蛋白缺失率为56.0%(28/50) (x2=10.287,P=0.001).hMLH1蛋白缺失率与肿瘤分化程度和T分期相关,但与性别、年龄、肿瘤部位、N分期和M分期均无关.[结论]在结直肠癌组织中存在hMSH2和hMLH1蛋白缺失,且hMSH2和hMLH1蛋白缺失与肿瘤T分期和分化程度相关.检测hMLH1和hMSH2蛋白表达对预后判断有一定的参考价值. 相似文献
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目的 分析hMLH1和hMSH2在食管胃交界腺癌和远端胃癌中的表达情况,探讨其在不同部位胃癌发生发展中的可能意义.方法 采用免疫组织化学染色法,对比检测52例食管胃交界腺癌和17例远端胃癌hMLH1和hMSH2在蛋白水平上的表达情况,分析表达差异及其临床病理意义.结果 食管胃交界腺癌组织中,hMLH1和hMSH2蛋白表达率分别为55.8%(29/52)和63.5%(33/52),远端胃癌中hMLH1和hMSH2蛋白的表达率分别为41.2%(7/17)和70.6%(12/17),两者的阳性表达率差异无统计学意义(P>0.05).食管胃交界腺癌和远端胃癌hMLH1和hMSH2的表达与肿瘤的分化程度以及淋巴结转移均无明显相关性(P>0.05).结论 hMLH1和hMSH2并不是食管胃交界腺癌和远端胃癌发生机制差异性的关键分子. 相似文献
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胃癌的微卫星不稳定性与hMLH1基因启动子甲基化的关系 总被引:3,自引:0,他引:3
背景与目的:由于细胞错配修复功能缺陷而导致基因组微卫星序列高度不稳定是遗传性非息肉性大肠癌发生的主要原因。以往的研究表明胃癌组织也有错配修复蛋白表达的缺失,但错配修复基因突变频率却很低;而启动子的甲基化是肿瘤抑癌基因失活的主要途径,也可能是错配修复基因功能丧失的主要原因。本研究拟通过对胃癌组织的微卫星不稳定性的分析及对hMLH1基因启动子甲基化和蛋白表达的检测,对胃癌发病的分子机制进行探讨。方法:从52例胃癌患者的癌组织及其周围组织提取DNA,PCR扩增基因组的5个微卫星位点BAT-26、D17S261、D3S1283、D2S123和D3S1611,毛细管电泳后,判定胃癌组织的微卫星不稳定性;免疫组织化学方法检测hMLH1蛋白的表达;酶切法检测hMLH1基因启动子甲基化。结果:52例胃癌标本中微卫星高度不稳定13例,低度不稳定2例,稳定37例。微卫星高度不稳定的13例胃癌组织中,均检测到hMLH1基因启动子甲基化(100.0%);微卫星低度不稳定和微卫星稳定的39例胃癌组织中,hMLH1基因启动子甲基化仅1例(2.6%),前者发生率高于后者,两者之间有显著性差异(P<0.01)。微卫星高度不稳定的13例胃癌的癌旁组织中,hMLH1基因启动子甲基化6例(46.2%),而微卫星低度不稳定和微卫星稳定39例胃癌的癌旁肿瘤组织标本中,hMLH1基因启动子甲基 相似文献
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目的:探讨胃癌中幽门螺杆菌(Helicobacter pylori,Hpylori)对hMSH2和hMLH1基因表达的影响,方法:利用尿素酶快速检验法确定胃癌组织及同病例癌旁粘膜、胃镜非癌患者胃粘膜组织有无Hpylori感染;应用免疫组织化学方法检测所有标本的hMSH2、hMLH1蛋白的表达。结果:胃癌组的hMSH2蛋白阳性表达率显著高于癌旁组和非癌组(P〈0.05);而后两者无显著差别(P〉0.05)。胃癌组、癌旁组和非癌组的hMLH1蛋白阳性表达率无显著差别(P〉0.05)。胃癌组织中,Hpylori感染组的hMSH2蛋白阳性表达率和hMLH1蛋白阳性表达率均显著低于非感染组(P〈0.05);癌旁组织中.Hpylori感染组的hMSH2蛋白阳性表达率和hMLH1蛋白阳性表达率均显著低于非感染组(P〈0.05);非癌患者胃粘膜中,H pylori感染组与非感染组的hMSH2蛋白阳性表达率及hMLH1蛋白阳性表达率均无显著差别(P〉0.05)。结论:胃粘膜hMSH2蛋白表达上调并hMLH1蛋白表达下调可能是胃癌发生的标志;Hpylori感染导致的胃粘膜细胞hMSH2和hMLH1蛋白表达降低,可能是促进胃癌发生的一个因素. 相似文献
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Expression of hMLH1 is inactivated in the gastric adenomas with enhanced microsatellite instability. 总被引:8,自引:0,他引:8
M J Baek H Kang S E Kim J H Park J S Lee Y K Paik H Kim 《British journal of cancer》2001,85(8):1147-1152
Microsatellite instability (MSI) and frameshift mutations in the genes containing coding nucleotide repeats have been reported in a subset of gastric adenomas, however the inactivation profiles of DNA mismatch repair genes in MSI-positive gastric adenomas have not been characterized. To address the origin of MSI in gastric adenomas, expressions of hMLH1 and hMSH2 were explored in 86 gastric adenomas. Gastric carcinomas, of which 16 were MSI-positive and 22 MSI-negative, were used as controls. MSI was found in 15 (17%) of gastric adenomas. Absent or decreased hMLH1 expression by immunohistochemistry was noted in most of the MSI-positive adenomas (13/15, 87%) and carcinomas (14/16, 88%), and all of these tumours showed methylation of the hMLH1 gene promoter. In contrast, rare inactivation of hMLH1 expression was found in MSI-negative adenomas (3/71, 4%) and carcinomas (2/22, 9%). Intense expression of hMSH2 gene product was observed in most of the gastric adenomas and carcinomas regardless of MSI status. These findings indicate that the inactivation of hMLH1 gene expression by promoter methylation is an early event and might be the origin of MSI-positive gastric adenomas. 相似文献
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SHEN Lü 《中国肿瘤临床(英文版)》2005,2(4):700-705
OBJECTIVE To study the effect of X-radiation on expression of hMSH2 and hMLH1 in nasopharyngeal carcinoma (NPC) CNE-1 cells, and explore the mechanism of DNA mismatch repair after radiation. METHODS The cells were divided into experimental and control groups. Experimental cells were exposed to 10 Gy radiation administered as 2 Gy per fraction. Control cells were not radiated. The distribution of cells in the cell cycle was analyzed using flow cytometry. The expression of hMSH2 and hMLH1 was examined by RT-PCR and Western blots. RESULTS The expression of hMSH2 mRNA in experimental cells was significantly greater compared to control cells at 0-3rd weeks and decreased at the 4th week following radiation (P〈0.01). The expression of hMSH2 protein in experimental cells was up-regulated and significantly greater compared to control cells at the 2nd-4th weeks after radiation (P〈0.01). There were no significant differences in hMLH1 mRNA and protein expression between experimental and control cells (P 〉0.05). CONCLUSION Radiation induces hMSH2 expression; hMSH2 has a role in the process of DNA repair, which maybe responsible for reduction of radiosensitivity after radiation. 相似文献
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目的 探讨程序性死亡配体 1(PD L1)、程序性死亡受体 1(PD 1)、错配修复基因hMSH2、hMLH1在胃癌表达及其与临床病理特征的关系。
方法 应用免疫组化法检测76例胃癌组织中PD L1、PD 1和hMSH2、hMLH1蛋白表达。
结果 胃癌组织中,PD L1表达水平与TNM分期、分化程度、淋巴结转移情况及脉管癌栓相关(均P<005);PD 1表达与各临床病例特征均无相关(P>005)。hMSH2、hMLH1表达与TNM分期相关(P<005)。PD L1与hMSH2、hMLH1蛋白表达相关(均P<005),PD 1与hMSH2、hMLH1蛋白表达均无相关,PD L1表达与PD 1无相关(P>005)。
结论 依据错配修复缺陷基因及PD L1表达水平选择性阻断PD L1/PD 1免疫检查点有望成为胃癌个体化免疫治疗的新策略。 相似文献
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Differential expression of hMLH1 and hMSH2 is related to bladder cancer grade,stage and prognosis but not microsatellite instability 总被引:6,自引:0,他引:6
Catto JW Xinarianos G Burton JL Meuth M Hamdy FC 《International journal of cancer. Journal international du cancer》2003,105(4):484-490
Defects in the DNA mismatch repair proteins result in microsatellite instability and malignancy in hereditary non-polyposis colorectal carcinoma (HNPCC). However, the role of mismatch repair (MMR) proteins and microsatellite instability (MSI) in transitional cell carcinoma of the bladder is less clear. In our study, the expression of 2 MMR proteins and the frequency of MSI in Transitional cell carcinoma of the bladder (TCC) were investigated. One hundred eleven patients with TCC of the bladder were studied, with complete clinicopathological data (median follow up of 5 years, range 5-16 years). Immunohistochemistry was used to detect the expression levels of hMLH1 and hMSH2. Microsatellite analysis for 14 loci (10 loci from the Bethesda consensus panel and the repeats in the TGFbetaR2, BAX, hMSH3 and hMSH6 genes) was performed on 84 tumors. Reduced expression of either MMR protein was seen in 26 of 111 tumors (23%). Reduced expression was seen more commonly in muscle invasive (p<0.03) and high grade TCC (p<0.03) than in superficial, low grade tumors. By 5 years, reduced expression of either MMR protein was associated with fewer recurrences of superficial tumors (p=0.015) and fewer relapses in all tumors (p=0.03), compared to tumors with normal expression. Nine tumors had reduced expression of both MMR proteins, analysis which suggests a synergistic reduction in expression (p=0.001). MMR expression was related to patient age, younger patients being more likely to have reduced MMR expression than older patients (p<0.01). MSI was seen at multiple loci in 1 tumor (1%) and at a single locus in 6 tumors (7%). MSI was not associated with MMR expression. Our findings indicate that reduced expression of the MMR proteins may have an important contribution in the development of a subset of TCCs and suggest a potential role for MMR expression as prognostic indicators. 相似文献
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目的 探讨错配修复基因hMLH1和hMSH2在散发性大肠癌(SCC)组织中的表达及其临床意义.方法 采用免疫组化Max Vision二步法对63例SCC标本中的癌组织、距癌灶3 cm以外的癌旁组织、距癌灶10 cm以外的正常组织中hMLH1和hMSH2蛋白的表达进行检测.结果 hMLH1蛋白在63例正常大肠组织、癌旁组织和SCC组织中的阳性表达率分别为95.2%、85.7%和81.0%,hMLH1蛋白在SCC组织中的阳性表达率明显低于正常大肠组织(P<0.05).hMSH2蛋白在63例正常大肠组织、癌旁组织和SCC组织中的阳性表达率分别为76.2%、66.7%和52.4%,hMSH2蛋白在SCC组织中的阳性表达率明显低于正常大肠组织(P<0.01).hMLH1蛋白在<60岁的SCC患者组织中的阳性表达率(100%)明显高于≥60岁的SCC患者组织(75.0%,P<0.05),在有淋巴结转移的SCC组织中的阳性表达率(50.0%)明显低于无淋巴结转移的SCC组织(93.3%,P<0.05).hMSH2蛋白在<60岁的SCC患者组织中的阳性表达率(80.0%)明显高于≥60岁的SCC患者组织(43.8%,P<0.05),在癌组织浸润至肠壁浆膜层SCC组织中的阳性表达率(61.5%)明显高于浸润至黏膜下层和肌层的SCC组织(37.5%,P<0.05).SCC组织中hMLH1和hMSH2蛋白的表达呈正相关关系(r=0.254,P<0.01).结论 hMLH1和hMSH2蛋白在SCC组织中的表达均有一定的缺失,并且与患者的年龄、淋巴结转移和癌组织浸润的范围有关.hMLH1和hMSH2基因可以作为临床预测和判断SCC发生和发展有用的实验室指标. 相似文献
18.
错配修复蛋白hMSH2 hMLH1表达在胃癌发生中的作用及临床意义 总被引:3,自引:0,他引:3
目的:探讨错配修复蛋白hMSH2、hMLH1表达及其在细胞内表达位置对胃癌发生的影响及临床意义.方法:收集大连医科大学附属第一医院胃癌标本172例、癌旁胃粘膜标本151例,非癌患者胃粘膜标本34例.应用免疫组织化学方法检测每例胃粘膜标本hMSH2、hMLH1蛋白的表达情况(包括其在细胞内表达位置),应用χ^2检验,Speannan等级相关分析在SPSS13.0统计软件上作相关统计结果:胃癌、癌旁胃粘膜和非癌患者胃粘膜hMSH2蛋白表达率分别为69.8%(120/172)、49.7%(75/151)和32.4%(11/34),胃癌组显著高于后两组(P=0.000),而后两组间无显著性差异(P=0.067);hMLH1蛋白表达率分别为73.3%(126/172)、57.6%(87/151)和41.2%(14/34),胃癌组显著高于后两组(P=0.000),而后两组间无显著性差异(P=-0.082).hMSH2和hMLH1蛋白表达率与胃癌患者的性别、年龄及胃癌分化程度均无显著相关关系.胃癌、癌旁胃粘膜和非癌患者胃粘膜hMSH2蛋白细胞核表达率分别为70.0%(84/120)、58.7%(44/75)和36.4%(4/11),细胞浆表达率分别为30.0%(36/120)、41.3%(31/75)和63.6%(7/11);胃癌、癌旁胃粘膜、非癌患者胃粘膜中,hMSH2蛋白细胞核表达率逐渐降低,而细胞浆表达率则逐渐增高(r=0.161,P=0.020)。三种不同胃粘膜间,hMLH1蛋白在细胞内表达位置无显著性差异(P=0.878)。结论:同时检测胃粘膜错配修复蛋白hMSH2和hMLH1的表达及其细胞内表达位置可能有助于胃癌的早期预警。 相似文献
19.
Y Wang J Irish C MacMillan D Brown Y Xuan C Boyington P Gullane S Kamel-Reid 《International journal of cancer. Journal international du cancer》2001,93(3):353-360
The most prevalent risk factors in the development of head-and-neck squamous-cell carcinoma (HNSCC) are excessive tobacco and alcohol consumption. In young patients with HNSCC, these risk factors are often absent. Our purpose was to investigate the risk factors, microsatellite instability (MSI) changes and status of the mismatch repair genes hMLH1 and hMSH2 in a cohort of young patients with HNSCC. Fifty-seven HNSCC tumors were examined for the presence of MSI at 16 microsatellite sites using PCR. In the young patient group (24 cases, < or = 44 years old), 100% of tumors had MSI at 1 site at least and 88% had MSI at 2 or more loci. In older patients (33 cases, > or = 45 years), MSI at 1 or more sites was found in 61% of tumors (young vs. old, p = 0.0003) and instability at 2 or more sites was found in 36% of tumors (young vs. old, p = 0.0001). The involvement of the mismatch repair genes was investigated by examining promoter methylation, exon mutation and gene expression of hMLH1 and hMSH2. All results were negative, indicating that inactivation of these 2 genes does not play a role in the development of MSI in tumors from this patient group. Furthermore, the young patient group had a significantly lower incidence of smoking (46% young, 88% old; p = 0.001) and alcohol consumption (33% young, 67% old; p = 0.0169), emphasizing the probable importance of other environmental and/or genetic factors in the development of their disease. 相似文献