食管鳞癌及癌旁粘膜中核转录因子κB p65及IκBα基因和蛋白表达及意义

目的:探讨核转录因子κB(NF-κB)p65基因及其抑制基因IκBα的表达与食管鳞癌发生的关系。方法:用RT-PCR及免疫组化SP法检测了61例食管鳞癌及其正常粘膜上皮、癌旁粘膜上皮中NF-κBp65基因、IκBα基因mRNA及蛋白的表达。结果:食管鳞癌中p65mRNA、IκBαmRNA的表达量明显高于正常上皮(P<0.01),p65蛋白、IκBα蛋白胞浆表达或胞核表达率均明显高于正常上皮(P<0.01)。癌旁粘膜中,NF-κBp65蛋白、IκBα蛋白在癌旁正常上皮中的胞浆或胞核阳性率均明显低于不典型增生上皮、原位癌和浸润癌(P均<0.05)。结论:NF-κBp65、IκBαmRNA表达和蛋白表达均与食管鳞癌的发生有关。     

Ⅱ型环氧合酶和CDK4在食管鳞癌中的表达及意义

目的 探讨Ⅱ型环氧合酶(COX-2)和CDK4在食管鳞癌中的表达与食管鳞癌的发生、浸润及转移的关系.方法 采用免疫组化S-P法检测49例食管鳞癌及癌旁黏膜组织中的表达.结果 COX-2在癌旁正常上皮、单纯增生上皮、轻度不典型增生上皮、重度不典型增生上皮、原位癌和浸润癌组织中的阳性表达率分别为0%(0/25)、7.1%(2/28)、33.3%(7/21)、50.0%(5/10)、69.2%(9/13)和73.5%(36/49).正常上皮组织与单纯增生上皮比较差异没有统计学意义(P＞0.05),但与轻度不典型增生上皮、重度不典型增生上皮、原位癌和浸润癌组织比较差异有统计学意义(P＜0.01).其在食管鳞癌中的阳性率与癌组织分级有关(P＜0.05).CDK4蛋白在癌旁正常上皮、单纯增生上皮、轻度不典型增生上皮、重度不典型增生上皮、原位癌和浸润癌组织中的阳性表达率分别为8%(2/25)、21.4%(6/28)、42.9%(9/21)、70%(7/10)、61.5%(8/13)和91.8%(45/49).正常上皮组织与单纯增生上皮比较差异没有统计学意义(P＞0.05),但与轻度不典型增生上皮、重度不典型增生上皮、原位癌和浸润癌组织比较差异有统计学意义(P＜0.01).CDK4阳性率与鳞癌分级无关(P＞0.05).COX-2、CDK4蛋白表达与食管鳞癌的浸润深度和淋巴结转移无关(P＞0.05).食管鳞癌组织中COX-2、CDK4蛋白阳性率有正相关性(P＜0.01).结论 COX-2、CDK4蛋白表达与食管鳞癌的发生有关.     

口腔癌前损害和鳞癌组织hMSH2转录水平改变与意义

目的 检测口腔癌前损害和鳞癌组织中hMSH2基因转录水平,探讨hMSH2在口腔鳞癌发生发展过程中的作用。方法 RT-PCR法选择性扩增11例口腔鳞癌及其癌前损害、正常组织hM-SH2 mRNA片段(316bp),以GAPDH(580bp)为内参对照,半定量测定hMSH2基因的mRNA转录水平。结果 口腔鳞癌的hMSH2转录水平较正常组织和癌旁组织显著升高(P<0.05),正常组织与癌旁组织的hMSH2基因转录水平差异无显著性(P>0.05)。结论 在口腔鳞癌的发生发展过程中,hMSH2基因的转录存在表观遗传学调节。     

口腔鳞癌及癌前病变组织中iNOS基因的表达

背景与目的:通过检测口腔鳞癌及癌前病变组织中诱导型-氧化氮合酶(inducible nitric oxide synthase,iNOS)mRNA及其蛋白产物的表达情况,探讨iNOS基因在口腔鳞癌发生、发展过程中的作用.材料与方法:应用免疫组化(SABC法)和原位杂交(ISH)2种方法分别检测10例正常13腔黏膜、12例上皮单纯增生、28例上皮不典型增生及32例口腔鳞癌组织中iNOS蛋白和iNOSmRNA的表达.结果:iNOS蛋白及iNOS mRNA均表达于细胞浆.正常口腔黏膜组织中未发现iNOS蛋白及iNOS mRNA表达;上皮单纯增生组、上皮不典型增生组、13腔鳞癌组中iNOS基因用免疫组化法检测的阳性表达率分别为16.67%(2/12)、67.86%(19/28)和78.13%(25/32),用原位杂交方法分别为16.67%(2/12)、71.43%(20/28)和75%(24/32),免疫组化和原位杂交检测的结果显示两者具有良好的一致性;上述4组不同口腔黏膜组织中iNOS蛋白与iNOS mRNA表达差异有统计学意义(P＜0.01);随着上皮不典型增生程度的加重,iNOS蛋白及iNOS mRNA表达均显著增强(P＜0.05);但口腔鳞癌组与上皮不典型增生组之间iNOS蛋白及iNOS mRNA阳性表达差异均无统计学意义(P＞0.05).结论:iNOS基因在口腔黏膜上皮组织中的表达可能与口腔鳞癌的发生发展中起重要作用,对iNOS基因的检测可为口腔鳞癌早期诊断提供依据.     

E-cadherin和β-catenin在食管鳞癌组织中的表达及其临床病理学意义

背景与目的:上皮性钙黏附蛋白(E-cadherin)不仅在介导钙离子依赖的同型细胞间的黏附中发挥作用,而且在细胞的迁徙和肿瘤浸润转移方面也有着重要的作用.许多研究表明,E-cadherin是作为一种抑癌基因发挥作用的.而最近研究表明,和E-cadherin相反,β-连环蛋白(β-catenin)在促进肿瘤的浸润转移方面具有重要作用.本研究重点探讨E-cadherin和β-catenin在食管鳞癌组织中的表达及其临床病理意义.方法:采用免疫组织化学PV法检测62例食管鳞癌组织、31例癌旁不典型增生组织及62例正常食管黏膜组织中E-cadherin和β-catenin的蛋白表达.结果:(1)正常黏膜组织、癌旁不典型增生组织及食管鳞癌组织中E-cadherin的阳性表达率依次降低,分别为95.2%、71.0%、40.3%;随着正常食管黏膜组织向癌组织的转化,β-catenin的膜表达阳性率依次降低,而胞质表达阳性率则依次增高,在低分化癌组织中甚至出现了核表达;E-cadherin的阴性表达率及β-catenin的胞质阳性表达率与食管鳞癌的浸润深度、分化程度及淋巴结转移密切相关(P＜0.05).(2)E-cadherin和β-catenin在食管鳞癌组织中的表达呈负相关(r=-0.453,P＜0.05).结论:食管鳞癌组织中E-cadherin的低表达及β-catenin的胞质高表达与食管鳞癌的浸润、转移有密切的关系.     

hMLH1和hMSH2蛋白在梨状窝癌手术切缘中的表达

目的:探讨梨状窝癌手术切缘的安全范围。方法:采用免疫组化法检测50例梨状窝癌组织、癌旁3mm、5mm、10mm和20例正常喉组织中hMLH1和hMSH2蛋白的表达。结果:hMLH1和hMSH2蛋白的阳性表达按癌组织、癌旁3mm、5mm、10mm和正常喉组织的顺序依次递增,越靠近正常组织,阳性表达越高。差异具有显著性(P<0.05)。结论:梨状窝癌手术可以选择距肿瘤10mm作为安全切缘参考标准。     

错配修复基因hMLH1和hMSH2在散发性大肠癌中的表达及其意义

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.     

p53和hMSH2蛋白在甲状腺乳头状癌组织表达的意义

目的:探讨抑癌基因p53和错配修复基因hMSH2 蛋白在甲状腺乳头状癌和结节性甲状腺肿(简称结甲)组织中表达的意义.方法:用免疫组织化学链霉菌抗生物素过氧化物酶(SP)法检测65例甲状腺乳头状癌及其21例癌旁结甲、14例单纯性结甲和7例甲状腺瘤组织中p53和 hMSH2 蛋白的表达.结果:p53蛋白在甲状腺乳头状癌组织中表达率35.38%明显高于癌旁结甲9.52%和单纯结甲7.14%(P＜0.05),但与甲状腺瘤42.86%无显著性差异; p53 蛋白在有淋巴结转移组表达率53.85%明显高于无淋巴结转移组30.77%(P＜0.05).hMSH2 蛋白在甲状腺乳头状癌组织表达率72.31%明显高于癌旁结甲52.38%(P＜0.05)、单纯结甲21.43%(P＜0.01)和甲状腺瘤28.57%(P<0.01);hMSH2 蛋白在有淋巴结转移组表达率76.92%与无淋巴结转移组71.15%无显著性差异(P＞0.05).p53 蛋白阳性组甲状腺乳头状癌hMSH2蛋白阳性表达率82.61%,阴性组66.67%,两种蛋白表达呈正相关(P＜0.05).结论:甲状腺癌细胞的异常增生可能导致碱基错配的增多继而导致p53突变的积累,是甲状腺乳头状癌发生的原因之一,hMSH2 蛋白高表达可能是甲状腺癌发生的一个早期标志.     

GLUT1在口腔鳞状细胞癌组织中的表达和意义

目的 探讨GLUT1表达与口腔鳞状细胞癌发生、发展及其生物学行为的关系.方法 应用免疫组化S-P法检测52例口腔鳞状细胞癌组织及其癌旁不典型增生组织、切缘正常黏膜组织中GLUT1的表达.结果 免疫组化阳性信号定位于细胞膜中,GLUT1在口腔鳞癌组织、癌旁不典型增生组织及正常口腔黏膜组织中的阳性表达率分别为88.46%、54.84%和19.23%,3组间两两比较,差异均有统计学意义(P<0.01).结论 GLUT1可能参与了口腔鳞状细胞癌的发生和发展过程.     

EHD2蛋白在食管鳞状细胞癌组织中的表达及意义

目的:探讨EHD2蛋白在食管鳞状细胞癌(esophageal squamous cell carcinoma,ESCC)组织中的表达情况及意义。方法:采用Western blot技术和免疫组织化学法(SP法)检测ESCC和相应癌旁正常组织EHD2蛋白的表达水平,分析其表达与患者临床病理学参数的关系。结果:在8对新鲜食管鳞癌组织中,EHD2蛋白在食管鳞癌组织中的表达明显低于癌旁正常组织(P<0.01);在44例石蜡标本中,EHD2蛋白在食管鳞癌组织的阳性表达率明显低于癌旁正常组织(P<0.05),且EHD2蛋白的表达明显与有无淋巴结转移(P=0.006)和组织分化程度相关(P=0.023),与患者的年龄、性别、肿瘤大小和TNM分期无相关性(P>0.05)。结论:EHD2蛋白在食管鳞癌组织中低表达,提示EHD2蛋白可能是新的食管鳞癌抑癌因子,并有望为食管鳞癌的预后判断和治疗提供新的思路。     

GLUT1表达与食管癌转移关系的研究

目的探讨GLUT1表达与食管癌发生、发展及其生物学行为的关系。方法应用免疫组化S_P法检测60例食管癌及其癌旁不典型增生组织、上切缘中正常食管黏膜中GLUT1的表达。结果免疫组化阳性信号均定位于细胞膜、胞浆中,GLUT1在食管癌癌组织、癌旁不典型增生组织及正常食管黏膜组织中的阳性表达率分别为91.67%、58.82%和20.00%,3组间两两比较,差异均有统计学意义(P<0.01);3组的强阳性表达率分别为78.18%、40.00%和8.33%,3组间两两比较,差异亦均有统计学意义(P<0.05或P<0.01)。结论GLUT1参与食管癌的发生、发展以及淋巴结转移。     

Cyclical change of hMSH2 protein expression in normal endometrium during the menstrual cycle and its overexpression in endometrial hyperplasia and sporadic endometrial carcinoma

BACKGROUND: The role of hMSH2 protein, one of the major DNA repair proteins, until now, had not been elucidated in terms of normal endometrial function during the menstrual cycle. The current study was designed to address this issue and to determine whether the expression of hMSH2 is altered in the course of endometrial carcinogenesis. METHODS: Immunohistochemical reactivity with a monoclonal antibody against the hMSH2 protein was examined in endometrial tissue specimens from 45 patients with normal endometrium, 51 patients with endometrial hyperplasia, and 27 patients with endometrial carcinoma. Immunohistochemical expression of proliferating cell nuclear antigen (PCNA) also was studied in the same samples as a measure of the proliferative activity and was compared with hMSH2 expression in each sample. RESULTS: The functional layer of normal endometrium displayed cyclic changes in hMSH2 protein expression during the menstrual cycle, showing positive expression in the proliferative phase and becoming weak to negative in the secretory phase. This expression pattern was similar to that of PCNA. Sixty-three percent of endometrial carcinomas showed strong positivity for both hMSH2 and PCNA expression, and 7.4% had an intensity of hMSH2 protein expression similar to that found in normal proliferative endometrial glandular cells. There was only 1 sample (3.7%) that was completely negative for hMSH2 expression, and 26% of samples were weakly positive for PCNA and hMSH2 protein. All simple hyperplasias and the majority of complex and atypical hyperplasias showed positive immunoreactivity for hMSH2 and PCNA. CONCLUSIONS: This study demonstrates that hMSH2 protein expression changes during the menstrual cycle in parallel with proliferative activity. In most patients with sporadic endometrial carcinoma, the expression of hMSH2 protein is consistent with PCNA expression. In contrast, loss of hMSH2 expression is observed rarely in patients with sporadic endometrial carcinoma.     

Angiopoietin-2和VEGF在口腔鳞癌中的表达及意义

目的研究口腔鳞癌组织中Ang-2和VEGF的表达并分析它们与肿瘤临床病理学特征和血管生成及血管成熟间的关系。方法:用常规的免疫组织化学的方法检测41例口腔鳞癌及30例癌旁正常组织和10例正常口腔黏膜中的Ang-2及VEGF的表达;通过双标免疫组织化学法同时染CD34(标记所有血管内皮细胞)和α-平滑肌肌动蛋白(标记血管壁细胞包括血管平滑肌细胞和周细胞)评估微血管密度(MVD)及血管成熟指数(VMI)。结果在口腔鳞癌组织中Ang-2和VEGF的阳性表达率分别为21(51.22%)和26(63.42%);Ang-2和VEGF在口腔鳞癌组织中表达显著高于它们在癌旁正常组织(P<0.05)和正常口腔黏膜组织中的表达(P<0.05);Ang-2表达与肿瘤的淋巴结转移密切相关(P<0.01)而VEGF表达与肿瘤的肿瘤分化程度相关(P<0.05),它们与病人的性别、年龄及TNM分期无关(P>0.05);Ang-2和VEGF表达阳性的鳞癌组织MVD显著高于它们阴性表达组(P<0.05)而Ang-2表达阳性的鳞癌组织VMI显著低于Ang-2表达阴性组(P<0.05)。在联合VEGF表达的情况下,同时表达Ang-2和VEGF的肿瘤MVD(51.08±2.99)显著高于其他任何表达状况(P<0.05)。结论Ang-2和VEGF在口腔鳞癌组织中的过表达可能在口腔鳞癌的进展过程中起重要作用;它们与肿瘤的血管生成和成熟密切有关。     

蛋白酪氨酸磷酸酶基因、血管内皮生长因子在口腔鳞状细胞癌组织中的表达及意义

目的:探讨口腔鳞状细胞癌（OSCC）组织中的蛋白酪氨酸磷酸酶基因（PTEN）、血管内皮生长因子（VEGF）的表达及意义。方法:选取我院2015年4月至2017年9月获取的90例OSCC患者的肿瘤组织标本（OSCC组）和45例癌旁正常口腔黏膜组织标本（对照组）,采用免疫组织化学染色技术检测两组标本中PTEN蛋白、VEGF蛋白的表达情况,并分析不同病理学分级、临床分期、淋巴结转移的OSCC患者肿瘤组织中PTEN蛋白、VEGF蛋白阳性表达差异。结果:OSCC组标本中PTEN、VEGF蛋白阳性表达率分别为35.56%、75.56%,对照组标本中PTEN、VEGF蛋白阳性表达率分别为73.33%、31.11%,两组比较差异具有统计学意义（P＜0.05）;在Ⅲ期和Ⅳ期、低分化、发生淋巴结转移的OSCC患者组织中PTEN蛋白阳性表达率显著低于Ⅰ期和Ⅱ期、高分化和中分化、未发生淋巴结转移的OSCC患者,差异均具有统计学意义（P＜0.05）;在Ⅲ期和Ⅳ期、低分化、发生淋巴结转移的OSCC患者组织中VEGF蛋白阳性表达率显著高于Ⅰ期和Ⅱ期、高分化和中分化、未发生淋巴结转移的OSCC患者,差异均具有统计学意义（P＜0.05）。结论:OSCC组织中PTEN蛋白表达水平显著降低,VEGF蛋白表达水平显著升高,并且与肿瘤的发生发展关系密切。     

G蛋白偶联受体激酶3在口腔鳞状细胞癌细胞增殖、迁移和侵袭中的作用及其可能的机制

目的:探讨沉默G蛋白偶联受体激酶3(G protein-coupled receptor kinase 3,GRK3)对口腔鳞状细胞癌(oral squamous cell carcinoma,OSCC)细胞增殖、迁移和侵袭的影响及其可能的机制.方法:利用Oncomine数据库分析GRK3在正常口腔组织及OSCC组织中...     

人口腔鳞状细胞癌组织中N-Cadherin蛋白的表达及临床意义

目的 探讨神经型钙黏附蛋白(N-cadherin)在人口腔鳞状细胞癌(OSCC)组织中的表达及其临床意义.方法 采用免疫组织化学方法 分别检测85例正常口腔上皮组织、62例癌旁不典型增生组织及85例OSCC组织中N-cadherin蛋白的表达,并分析其与临床病理学参数之间的关系.结果 N-cadhedn蛋白在OSCC组...     

Differential expression of the mismatch repair gene hMSH2 in malignant prostate tissue is associated with cancer recurrence

BACKGROUND: Mismatch repair (MMR) genes are responsible for coordinated correction of misincorporated nucleotides formed during DNA replication. Inactivating mutations in MMR genes have been described in sporadic cancers and a hereditary cancer predisposition syndrome. Mismatch repair deficiency causes instability at microsatellites and increased mutation rates. Although microsatellite instability (MSI) has been described in high-grade and lymph node positive prostate carcinoma specimens, an analysis comparing hMSH2 expression, MSI, and outcome in clinically organ confined prostate carcinoma has not been reported. METHODS: Immunohistochemical analysis of benign and malignant prostate tissue from 101 patients was performed using a monoclonal antibody specific for the hMSH2 protein. Expression was correlated with MSI using dinucleotide repeat markers and laser-captured microdissected DNA from normal and tumor cells. hMSH2 protein expression and MSI were assessed with respect to pathologic stage, Gleason score, and time to detectable serum prostate specific antigen (PSA) after prostatectomy in patients with clinically localized prostate carcinoma. RESULTS: In normal glands, hMSH2 staining was minimal to low and confined to the basal cell layer. In 32% of benign prostatic hyperplasia cases, hMSH2 staining was increased in the basal and luminal cell layers whereas 71% of cancer specimens had uniform moderate to high staining. Microsatellite instability was detected in 60% of absent to low staining and 26% of moderate to high staining prostate carcinoma specimens. Differential staining in benign versus malignant prostate tissues was statistically significant (P < 0.001) as was the correlation between absent to low hMSH2 staining and presence of MSI (P = 0.028). Decreased risk for PSA recurrence after radical prostatectomy correlated with absent to low hMSH2 staining in malignant prostate tissue but was only marginally significant (P = 0.05 for 24 month recurrence and P = 0.08 for overall time to PSA recurrence). CONCLUSIONS: The results of the current study demonstrate differential hMSH2 expression in benign and malignant prostate tissue. Moreover, hMSH2 expression is altered in a subset of clinically localized prostate carcinoma specimens independent of pathologic stage and Gleason pattern. A statistically significant correlation between hMSH2 immunohistochemical staining intensity and MSI also was identified in prostate carcinoma specimens. Furthermore, the time to cancer recurrence as determined by detectable serum PSA after prostatectomy was associated with hMSH2 staining intensity. Taken together, our results suggest that hMSH2 gene expression in prostate carcinoma may be a useful prognostic marker for outcome in men with clinically organ confined prostate carcinoma.     

Inactivation of human mutL homolog 1 and mutS homolog 2 genes in head and neck squamous cell carcinoma tumors and leukoplakia samples by promoter hypermethylation and its relation with microsatellite instability phenotype

BACKGROUND: A subset of head and neck squamous cell carcinoma (HNSCC) exhibits a microsatellite instability (MIN) phenotype. The authors correlated alterations in the mismatch-repair genes human mutL homolog 1 (hMLH1) and human mutS homolog 2 (hMSH2) in primary head and neck squamous cell carcinoma (HNSCC) tumors and in samples of leukoplakia with the MIN phenotype. METHODS: One hundred twenty-three paired HNSCC normal and tumor tissues and 27 leukoplakia samples were examined for hypermethylation of hMLH1 and hMSH2 promoters. The hypermethylation status of the tissues was confirmed by expression studies. Sixty-three of 123 randomly selected tumors and all 27 leukplakia samples were genotyped with 8 microsatellite markers to determine MIN. RESULTS: Fifty percent of HNSCC tumors and 63% of leukoplakia samples harbored hypermethylation at either or both hMLH1 and hMSH2 promoters. Normal tissues adjacent to methylation-positive tumors also demonstrated hypermethylation of both promoters at a high frequency (25%). A positive correlation between tobacco habit and promoter hypermethylation was observed (P = .001). A correlation was observed between MIN and the frequency of promoter hypermethylation in the leukoplakia samples, but no such trend was observed in the HNSCC tumors. It is noteworthy that patients who had a high frequency of MIN-positive tumors exhibited hypermethylation in both the affected tissues and the adjacent normal tissues (P = .007). Patients with a tobacco habit who had promoter hypermethylation at both the affected tissues and the adjacent normal tissues had tumors that mostly were MIN positive (P = .047). CONCLUSIONS: The current results suggested that tobacco-addicted individuals are more susceptible to promoter hypermethylation of hMLH1 and hMSH2 and that, if such hypermethylation occurs in the normal squamous epithelium of the head and neck region, then those tissues are likely to develop into tumors that involve the MIN pathway.