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目的:探讨hMLH1和hMSH2蛋白缺失与Ⅱ和Ⅲ期结直肠癌患者临床病理特征及预后的关系。方法:选取162例行结直肠癌根治术的患者,采用免疫组化方法检测患者hMLH1和hMSH2蛋白表达情况,采用χ2检验分析hMLH1和hMSH2蛋白表达缺失与结直肠癌临床病理特征之间的关系;采用Kaplan-Meier生存曲线、Log-Rank检验、Cox风险回归模型分析不同因素与预后的关系。结果:1)hMLH1蛋白的表达缺失率为38.89%,hMSH2蛋白的表达缺失率为21.60%。2)hMLH1和(或)hMSH2蛋白表达缺失的患者较hMLH1和hMSH2蛋白表达无缺失的患者2年无瘤生存率(DFS)高,P=0.023。3)hMLH1和(或)hMSH2蛋白缺失的患者与hMLH1和hMSH2蛋白表达无缺失的患者相比,前者多发病在右半结肠(P=0.018)、淋巴结转移数目较少(P=0.007)、多存在家族史(P=0.013),且TS蛋白多为低表达(P=0.004)。4)单因素分析显示,hMLH1和hMSH2蛋白表达情况(P=0.010)、TNM分期(P=0.010)、淋巴结转移数目(P=0.002)为结直肠癌患者预后的影响因素;多因素分析显示,hMLH1和hMSH2蛋白表达情况、淋巴结转移数目为结直肠癌患者预后的独立影响因素。结论:hMLH1和hMSH2蛋白表达缺失的结直肠癌患者具有独特的临床病理特征,预后较好,hMLH1和hMSH2蛋白表达缺失是预后的独立影响因素。 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: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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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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目的:探讨Ⅲ期散发性结肠腺癌错配修复(mismatchrepair,MMR)蛋白hMLHl、hMSH2表达状态与临床病理特征、FOLFOX方案辅助化疗疗效及预后关系。方法:收集2005—01—01—2007-12-31南通大学附属医院收治,临床及随访资料完整的散发性结肠癌根治术后Ⅲ期224例标本,免疫组化方法检测癌组织hMLHl和hMSH2蛋白的表达,分析MMR蛋白的表达与临床病理特征、FOLFOX方案辅助化疗疗效及预后的关系。结果:224例患者中,hMLHl蛋白表达缺失28例(12.5%),hMSH2蛋白表达缺失5例(2.2%),无2种蛋白同时表达缺失,2种蛋白表达缺失率合计为14.7%(33/224)。低分化癌组织中2种MMR蛋白的表达缺失率高于高中分化程度,P-0.046;右侧结肠癌2种MMR蛋白表达缺失率为23.2%(16/69),高于左侧结肠癌的11.0%(17/155),P—0.017。hMLHl和hMSH2蛋白表达状态与患者的年龄、性别和临床分期无关,P〉0.05。MMR蛋白表达缺失与正常患者5年无病生存率(disease—freesurvival,DFS)分别为72.7%和54.5%,差异有统计学意义,P=0.047;MMR蛋白表达缺失患者5年总生存率(overallsurvival,OS)为78.8%,高于表达正常患者的65.4%,但差异无统计学意义,P〉0.05。结论:hMLHl和hMSH2蛋白的表达状态有可能作为Ⅲ期散发性结肠腺癌FOLFOX方案辅助化疗疗效及预后预测的指标。 相似文献
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[目的]探讨子宫颈癌中错配修复基因表达产物对抑癌基因p53表达的影响.[方法]30例子宫颈炎标本及70例子宫颈鳞癌标本采用免疫组织化学S-P法检测hMLH1、hMSH2与p53的表达.[结果]子宫颈炎与子宫颈鳞癌组织hMLH1阳性表达率分别为60.0%(18/30)与55.7%(39/70);hMSH2阳性表达率分别为23.3%(7/30)与57.1%(40/70);p53表达率分别为33.3%(10/30)与61.4%(43/70).p53表达阳性和阴性组的子宫颈癌hMLH1阳性表达率分别为46.5%(20/43)与40.7%(11/27),两者无相关性(rs=0.057,P=0.645);hMSH2阳性表达率分别为41.9%(18/43)与18.5%(5/27),两者存在显著相关性(rs=0.242,P=0.044).[结论]子宫颈炎向宫颈癌的发展中碱基错配逐渐增多,hMSH2蛋白的高表达与p53的低表达对宫颈癌的预后具有一定的预测作用. 相似文献
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Han-Shui Hsu Chiao-Kai Wen Yen-An Tang Ruo-Kai Lin Wing-Yin Li Wen-Hu Hsu Yi-Ching Wang 《Clinical cancer research》2005,11(15):5410-5416
PURPOSE AND EXPERIMENTAL DESIGN: The etiologic association and prognostic significance of mismatch repair gene/protein alterations have never been examined in nonsmoking lung cancer. Therefore, we investigated protein expression and promoter hypermethylation of hMLH1 and hMSH2 genes in the tumor specimens from 105 nonsmoking female non-small cell lung cancer (NSCLC) patients. Immunohistochemistry and restriction enzyme-based multiplex PCR were used to examine the protein expression and promoter hypermethylation, respectively. The occurrence of gene/protein alteration for each gene was compared with the patients' clinicopathologic variables as well as the overall survival and cancer-specific survival rates. RESULTS: Protein expression alteration and promoter hypermethylation were observed in 66% to 67% and 30% to 34% of tumor specimens for hMLH1 and hMSH2 genes, respectively. Loss of hMLH1 and hMSH2 protein expression was significantly associated with their promoter hypermethylation (P < 0.0001 and P = 0.049). The overall survival and cancer-specific survival rates were significantly lower in patients with promoter hypermethylation of hMSH2 gene than in those without hypermethylation (P = 0.038 and P = 0.004). The poor prognosis was still especially significant in adenocarcinoma (P = 0.035 and P = 0.061) and early-stage NSCLC patients (P = 0.067 and P = 0.041). CONCLUSION: Our data suggest that hMLH1 is the major altered mismatch repair gene involved in nonsmoking NSCLC tumorigenesis and that promoter methylation is the predominant mechanism in hMLH1 and hMSH2 deregulation. In addition, promoter methylation of the hMSH2 gene may be a potential prognostic factor in nonsmoking female lung cancer. 相似文献
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We examined biological and clinicopathological significance of individual and combined hMLH1, hMSH2, hMSH3 and hMSH6 expression with immunohistochemistry in 301 unselected colorectal cancers. Weak hMLH1 expression was correlated to microsatellite instability (P=0.04), negative p53 expression (P=0.005) and mucinous carcinomas (P=0.02). Weak hMSH2 expression was related to negative ras (P<0.001) and p53 expression (P=0.005), and better survival (P=0.03). hMSH2, hMSH3 and hMSH6, as well as hMLH1, hMSH2, hMSH3 and hMSH6, were combined into a 'functional' and a 'less-functional' group, respectively. Both 'less-functional' groups were/tended to be associated with microsatellite instability, negative ras and p53 expression, and better survival. In summary, hMLH1 and hMSH2 were more important when investigated individually, and the combined groups were more related to the mutator pathway, suggesting that combined deficiencies of the proteins are more efficiently involved in the mutator pathway. Our result from weak versus strong staining may suggest that the intensity of staining should be considered in future studies on mismatch repair proteins. 相似文献
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Colorectal cancer (CRC) cell lines displaying microsatellite instability (MSI) are resistant to 5-fluorouracil in vitro, which can be overcome by restoring DNA mismatch repair (MMR) competence. Furthermore, elevated levels of Bcl-2 protein confers cytotoxic drug resistance to tumour cell lines. We examined the expression of Bcl-2 and two MMR proteins (hMLH1 and hMSH2) in advanced CRC patients, to determine their mutual relationship, association to therapeutic response and impact on disease outcome. Tumour samples from 73 CRC patients who were treated in advanced stage with either irinotecan alone or in combination with 5-FU/leucovorin, were analysed for expression of Bcl-2, hMLH1 and hMSH2 using immunohistochemistry. Bcl-2 expression was closely correlated with hMLH1 and hMSH2 expression (negative-weak/moderate-strong) (p=0.01). Bcl-2/MMR expression was significantly (p=0.030 for whole series; p=0.018 for the 5-FU-treated cases) related to the response to treatment; tumours with low levels of both Bcl-2 and MMR responded better (n=18/31, 58%) than those with high Bcl-2 and MMR (n=3/16, 18%). Patients with high Bcl-2/MMR expression had a significantly longer DFS (47 vs. 11 months, n=26) than those with low Bcl-2/MMR index (p=0.005). Bcl-2/MMR index was not significantly related to disease-specific survival or survival with metastases. The present data suggest that MSI patients with low Bcl-2/MMR demonstrate a significantly shorter DFS, whereas patients with high expression of the two markers obtain the greatest benefit from 5-FU-based chemotherapy. 相似文献
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目的 探讨人类错配修复基因hMLH1、hMSH2及增殖细胞核抗原PCNA在肺癌组织中的表达及意义。方法 运用免疫组织化学S P法对 5 6例肺癌组织中hMLH1、hMSH2及PCNA的表达进行检测。结果 5 6例肺癌组织中hMLH1的阳性表达率为 35 % ,hMSH2阳性表达率为 2 8.6 % ,分化程度高者阳性率显著高于分化程度低者 (P <0 .0 1) ,有淋巴结转移者hMLH1及hMSH2阳性率低于无淋巴结转移者 (P <0 .0 5 ) ,不同病理组织学类型之间hMLH1及hMSH2表达无显著差别 (P >0 .0 5 ) ;5 6例肺癌组织中分化程度低者PCNA标记指数高于分化程度高者 (P <0 .0 1) ,有淋巴结转移者PCNA标记指数高于无淋巴结转移者 (P <0 .0 5 ) ,hMLH1及hMSH2阴性表达者的PCNA标记指数明显高于hMLH1及hMSH2阳性表达者 (P <0 .0 1) ,不同病理组织学类型之间PCNA标记指数无显著差别 (P >0 .0 5 )。结论 hMLH1及hMSH2基因的缺陷及PCNA的表达与肺癌的发生发展过程并与分化程度及有否淋巴结转移有关 相似文献