食管鳞癌中p16基因启动子区甲基化及其表达

 目的探讨食管鳞癌（ESCC）p16基因甲基化的状况及其表达与食管鳞癌临床病理特征之间的关系。方法采用甲基化特异性PCR方法（MSP）分别检测75例食管癌组织、癌旁组织和切缘组织p16基因启动子区域CpG岛甲基化状态。采用Envision免疫组化法检测食管癌组织及癌旁组织的p16蛋白的表达。结果75例标本中，食管癌组织、癌旁组织和切缘细织p16基因甲基化率分别为41．3％（31／75）、13．3％（10／75）和6．67％（5／75）。癌组织和癌旁组织P16蛋白的阳性表达率分别为29．3％（22／75）和56．7％0（17／30）。31例癌组织p16基因甲基化阳性标本中有2例（6．4％）检测到P16蛋白的表达，而44例癌组织p16基因甲基化阴性标本中有20例（45．5％）检测到P16蛋白的表达。食管癌组织p16基因甲基化率显著高于癌旁组织和切缘组织（P〈0.01），P16蛋白表达与p16基因甲基化呈负相关。p16基因启动子区甲基化与食管癌的组织学分级、肿瘤部位无明显相关，与临床分期、淋巴转移密切相关。结论p16基因甲基化在食管癌发生发展中起着重要作用，食管鳞癌的分期和淋巴结转移与p16基因甲基化之间有密切关系。     

胆管癌p53-bax线粒体凋亡通路的甲基化研究

目的探讨胆管癌p53-bax线粒体凋亡通路中多个基因的甲基化状态及其在胆管癌发生过程中的意义。方法采用甲基化特异性聚合酶链反应（MSP），对胆管癌组织和癌旁组织中的p14^ARF、DAPK和TMS1／ASC基因启动子的甲基化状态进行检测，并对胆管癌组织中p53基因外显子5～8进行DNA序列分析。结果36例胆管癌组织标本中，有24例（66．7％）至少存在1个抑癌基因的甲基化，其中p14^ARF、DAPK和TMS1／ASC基因甲基化的比率分别为25．0％、30．6％和36．1％；癌旁组织中，有5例（13．9％）存在抑癌基因的甲基化，其中TMS1／ASC3例（8．3％），DAPK2例（5．6％）。36例胆管癌组织标本巾，有22例（61．1％）存在p53基因的突变。p53突变伴1个以上抑癌基因甲基化者共14例，占38．9％，其发生率与胆管癌的病理类型、分化程度和浸润深度有关（P〈0．05）。结论p53-bax线粒体凋亡通路中，DNA甲基化是胆管癌中常见的分子事件。癌旁组织中，DAPK和TMS1／ASC基因的甲基化率虽然较低，但可能有早期诊断意义。p53突变伴抑癌基因的甲基化与胆管癌的病理生物学行为有关，并趋向于较高的恶性程度。     

胃癌组织hMLH1启动子甲基化是造成其蛋白表达降低的主要原因

目的：通过研究胃癌中错配修复基因hMLH1启动子区5CpG岛甲基化及蛋白表达情况，探讨hMLH1启动子Ⅸ甲基化对蛋白表达的影响及在胃癌发病中的作用。方法：收集诊断明确且未经放化疗的胃癌手术切除标本41例及同病例癌旁黏膜。应用免疫组化SP法检测标本hMLH1蛋白表达情况。应用甲基化特异性PCR（MSP）榆测标本hMLH1启动子区甲基化情况。结果：胃癌组与癌旁组，hMLH1蛋白阳性表达率分别为58．54％（24／41）和80．49％（33／41）（P〈0．05）；启动子甲基化率分别为80．49％（33／41）和24．39％（10／41）（P〈0．05）；完全甲基化率分别为41．46％（17／41）和19．51％（8／41）（P〈0．05）；部分甲基化率分别为39．02％（16／41）和4．88％（2／41）（P〈0．05）。无论胃癌组织还是癌旁组织，完全甲基化病例均出现hMLH1蛋白表达缺失，部分甲基化病例和启动子未甲基化病例均有hMLH1蛋白表达。hMLHI基因启动子甲基化率与胃癌患者性别、年龄、癌组织分化程度、浸润深度和淋巴结转移均无明显相关性（P〉0．05）。结论：hM—LH1基因启动子甲基化是导致hMLH1蛋白表达降低的主要原因；胃黏膜hMLH1蛋白表达降低有助于胃癌的预警。     

肺癌中FHIT基因异常甲基化及其蛋白表达的意义

目的：检测肺癌组织FHIT蛋白表达及基因异常甲基化，探讨其在肺癌发生发展中的作用。方法：应用免疫组化SP法和甲基化特异性PCR（MSP）检测肺癌组织与癌旁组织（n=60）中FHIT蛋白表达和基因异常甲基化情况，并对基因甲基化扩增产物进行测序，对60例患者随访调查。结果：FHIT蛋白在癌旁组织的阳性表达明显高于癌组织，二者差异存在统计学意义（76．7％vs50．0％，P〈0．05）；FHIT基因异常甲基化在癌组织中的发生率明显高于癌旁组织，二者差异存在统计学意义（68．3％vs35．0％，P〈0．001）；FHIT基因甲基化的发生率在FHIT蛋白阴性患者中高于阳性表达者（83．3％vs53．5％，P〈0．05）；FHIT蛋白表达及基因甲基化发生率均与性别、年龄、吸烟状况、组织学类型、大体分型、TNM分期及淋巴结转移无关（P〉0．05）；FHIT蛋白阳性表达患者生存率高于阴性表达者（P〈0．05），FHIT蛋白是影响无瘤生存时间的危险因素（P〈0．001）。结论：肺癌中FHIT基因异常甲基化频繁发生，FHIT蛋白表达明显下调，FHIT在肺癌的发生发展中可能具有重要的作用，FHIT蛋白可以作为判断患者预后的重要指标。     

肺癌组织细胞FHIT 基因启动子甲基化和转录表达

 目的 探讨FHIT（fragile histidine triad，脆性组氨酸三联体）基因表达水平及其启动子CpG岛甲基化状态与肺癌发生发展的关系。方法 用实时定量PCR检测FHIT mRNA在肺癌组织、肺癌旁组织与去甲基化剂5-氮杂-2’-脱氧胞苷（5-Aza-2’-deoxycytidine、5-Aza—CdR）处理前后A549细胞株中的表达，用甲基化特异性PCR（MS-PCR）检测FHIT启动子CpG岛甲基化状态。结果 FHIT mRNA在肺癌旁组织中全部表达，在肺癌组织中表达缺失率为48．89％（22／45），且表达量低于正常肺组织（t=-15．851，P〈0．001），但在不同年龄和性别、肿瘤大小、恶性程度、肿瘤分类的差异无显著性；FHIT基因启动子在肺癌组织中发生甲基化的频率为40％（18／45）、在癌旁组织中频率8．7％（2／23）（X^2=7．184，P〈0．01），18份启动子区甲基化的肺癌标本中，10份同时伴有mRNA表达缺失。结论 在肺癌组织中，FHIT基因启动子甲基化频率明显升高，其表达缺失或下调，提示FHIT启动子甲基化可在肺癌发生和发展中起一定作用。     

PTEN基因甲基化及其表达异常与胃癌的关系

目的：探讨PTEN基因表达、启动子区甲基化与胃癌及其临床病理特征的关系。方法：采用甲基化特异性PCR法（MSP）和逆转录聚合酶链反应（RT—PCR）法，分析胃癌组织及相应癌旁正常组织中PTEN基因启动子区甲基化及其mRNA表达情况。结果：48．2％（27／56）的胃癌组织和3．6％（2／56）的癌旁胃组织PTEN基因启动子区发生甲基化．癌组织PTEN基因启动子区甲基化率显著增高（P〈0．05）：其中，2例甲基化癌旁胃组织均为胃癌组织中有甲基化的病例．发生淋巴结转移的29例胃癌组织中．19例PTEN基因启动子甲基化；发生淋巴结转移的PTEN基因启动子甲基化显著高于无淋巴结转移组（P〈0．05）。RT—PCR结果显示，所有甲基化的胃癌组织中PTEN mRNA均无表达，结论：胃癌中PTEN基因mRNA失表达与其启动子区甲基化有关，这可能是胃癌发生、发展以及转移的原因之一。     

STK15在肺鳞癌、腺癌中的表达及意义

背景与目的 丝氨酸／苏氨酸激酶15（serlnethreoninekinase15，STK15）是一种有丝分裂激酶。它的过表达出现在许多恶性肿瘤中，并与肿瘤的发生、发展有关，但其在肺癌组织中的表达和意义尚不清楚。本研究的目的是探讨STK15在肺鳞癌、腺癌中的表达及其与各临床病理特征的关系。方法 采用免疫组织化学方法检测80例肺鳞癌、腺癌及20例癌旁肺组织标本中STK15的蛋白表达，采用Westernblot和RT-PCR方法检测40例新鲜肺鳞癌、腺癌及癌旁肺组织标本中STK15蛋白及STK15mRNA的表达。结果免疫组化结果显示STK15蛋白在肺癌中的表达率为68．75％（55／80），明显高于癌旁肺组织（0／20）（P〈0．001）；STK15表达与肺癌的分化程度有密切关系（P=0．011），而与肺癌的TNM分期、组织学类型、淋巴结转移等均无明显关系（P〉0．05）。肺癌组织中STK15蛋白（P〈0．001）和STK15mRNA（P〈0．001）的相对表达量明显高于癌旁肺组织。结论STK15蛋白及STK15mRNA在肺鳞癌、腺癌中的表达明显高于癌旁肺组织。STK15蛋白的表达与肺癌的分化程度有密切关系，高分化者明显低于低分化者。     

NSCLC患者血清中p16、DAP基因甲基化的研究

目的：探讨p16、死亡相关蛋白激酶（death-associated protein kinase,DAP）基因的异常甲基化作为非小细胞肺癌（NSCLC）患者诊断的基因标志物的可行性。方法：采用甲基化特异性PCR（MSP）法检测30例NSCLC患者肿瘤组织及对应血清中p16、DAP基因的异常甲基化，结果：NCSLC肿瘤中60．0％（18／30）检测出至少一个基因启动子呈甲基化改变，在18例肿瘤组织检测到异常甲基化的患者中，50．0％的患者（9／18）在血清中检测到相应的改变。所有的癌旁组织、健康对照组的血清中及正常肺组织均未检测到p16、DAP的甲基化，结论：检测NSCLC患者血清中p16、DAP基因异常甲基化有可能成为肺癌诊断的分了标志物。     

脆性组氨酸三联体与肺癌的临床病理学研究

目的：探讨抑癌基因FHIT在肺癌组织中的表达缺失及其与临床病理因素的关系。方法-采用免疫组织化学S—P法检侧40例肺癌组织中FHIT蛋白表达情况,以癌旁组织作对照。结果：FHIT蛋白表达阴性率在肺癌为65．00％（26／40）,FHIT蛋白在肿瘤组织中的表达明显低于癌旁正常组织（P〈0．05）。其中鳞癌为38．46％（5／13）,腺癌为77．78％（21／27）,其差异有显著性（P=0．01）。FHIT与组织学类型、分化程度及性别有相关性（P〈0．05）。与年龄、肿瘤大小、临床分期、有无淋巴结转移无关（P〉0．05）。结论：FHIT在肺癌中失表达或表达下降可能与肺癌的发生有相关性。     

非小细胞肺癌组织中ERCCl及TUBB3基因mRNA的表达及其临床意义

目的：探讨ERCC1及TUBB3基因mRNA在非小细胞肺癌（NSCLC）组织、癌旁组织和良性组织中的表达,两者的关系及其与肺癌患者临床、病理等特征的关系。方法：采用逆转录-聚合酶链反应（RT-PCR）方法检测82例非小细胞肺癌组织、36例癌旁组织及15例良性组织中ERCC1及TUBB3基因mRNA的表达。结果：ERCC1和TUBB3基因在NSCLC患者癌、癌旁及良性组织中均有表达,ERCC1在这三种组织中阳性表达率分别为54．9％（45／82）、44．4％（16／36）及73．3％（11／15）,差异元统计学意义（P=0．165）;而TUBB3阳性表达率分别为18．3％（15／82）、2．8％（1／36）及93．3％（14／15）,三者差异有统计学意义（P=0．000）,癌组织表达率18．3％高于癌旁组织2．8％（P=0．048）。ERCC1基因在腺癌表达率63．O％（34／54）高于鳞癌39．3％（11／28）（P=0．041）。TUBB3基因在腺癌表达率25．9％（14／54）高于鳞癌3．6％（1／28）（P=0．013）。但是二者在其余临床和病理等特征方面的表达均无统计学意义。癌组织中ERCC1及TUBB3表达呈中度正相关（r=0．429,P=0．000）。结论：ERCC1及TUBB3基因mRNA在NSCLC中腺癌表达均高于鳞癌,并且二者在癌组织中表达有密切的关系。     

HYPERMETHYLATION OF p14^ARF PROMOTER REGION AND EXPRESION OF p14^ARF GENE PRODUCT IN NON-SMALL CELL LUNG CANCER

Objective： This study was designed to investigate promoter methylation status and protein expression of p14^ARF gene in non-small cell lung cancer, and value the role of p14^ARF promoter methylation in carcinogenesis of non-small cell lung cancer. Methods： Promoter methylation status and protein expression of p14^ARF gene in 40 cases of non-small cell lung cancer were analyzed by methylation specific polymerase china reaction （MSP）, restriction enzyme-related polymerase chain reaction （RE-PCR） and immunohistochemistry （IHC）. Results： The positive rates of p14^ARF promoter methylation in tumor tissues and normal tissues adjacent to cancer were 17.5% （7/40） and 2.5% （1/40） respectively. There were statistically significant differences between them, P〈0.05. The results of RE-PCR were consistent with that of MSP. The expression rate of p14^ARF protein in tumor tissues was significantly lower than that in normal tissues adjacent to cancer, p〈0.01. Promoter methylation status and protein expression of p14^ARF gene in non-small cell lung cancer showed significantly an inverse correlation （r=-0.56, P〈0.01）, and both of them did not relate statistically with the clinicopathologic characteristics of patients such as histological classification, clinical stage, differentiation grade and lymph node involvement. Conclusion： Promoter methylation is a crucial mechanism of inactivation of p14^ARF gene. Promoter methylation of p14^ARF gene might he involved in carcinogenesis of non-small cell lung cancer, and is an early event in development process of non-small cell lung cancer. It might be used as a new target in gene treatments in the future.     

肺癌p14ARF和p16INK4a基因协同表达缺失及其意义

目的：研究抑癌基因位点ＩＮＫ４ａ－ＡＲＦ在肺肿瘤细胞中的表达状况,揭示ｐ１４ＡＲＦ和ｐ１６ＩＮＫ４ａ协同表达缺失与肺癌发生发展的相关性。方法：用ＲＴ－ＰＣＲ和Ｗｅｓｔｅｒｎ ｂｌｏｔ对６株肺癌细胞（ＳＰＣ－Ａ－１,Ｃａｌｕ－１,Ｈ４４６,ＳＨ７７,Ａ５４９,Ｈ４６０）的ＩＮＫ－４ａ－ＡＲＦ基因位点在ｍＲＮＡ、蛋白水平上进行检测,对ＰＣＲ产物进行纯化和测序分析。结果：６株肺癌细胞中,有３株细胞（Ｈ４     

宫颈癌组织中DAPK基因启动子甲基化的研究

背景与目的:已有研究表明DNA异常甲基化在肿瘤的发生、发展中发挥了重要作用.本研究旨在探讨宫颈癌组织中DAPK(death-associated protein kinase)启动子甲基化与基因失活的关系.方法:应用甲基化特异性PCR (methylation-specific PCR,MSP)技术检测52例宫颈癌、60例宫颈上皮内瘤样病变(cervical intraepithelial neoplasia,CIN)和20例正常宫颈鳞状上皮DAPK启动子甲基化状况,应用免疫组化方法检测其蛋白表达;分析DAPK启动子甲基化和基因失活与宫颈癌临床病理因素之间的关系.结果:正常宫颈组织不存在DAPK基因启动子CpG岛甲基化,而CIN和宫颈癌中的DAPK甲基化率分别为18.3%(11/60)、65.4%(34/52),三者之间的差异有统计学意义(P<0.05).宫颈鳞癌的DAPK甲基化率明显高于腺癌(分别为80.0%和16.7%),其差异有统计学意义(P<0.001).DAPK启动子甲基化和DAPK蛋白表达之间呈负相关(r=-0.849,P<0.001).结论:DAPK启动子CpG岛甲基化可导致基因失活,并可能参与宫颈癌的发生.     

p16(INK4a) and histology-specific methylation of CpG islands by exposure to tobacco smoke in non-small cell lung cancer

The p16(INK4a) protein inhibits cyclin-dependent kinase 4, a key regulator of progression through the G(1) phase of the cell cycle. Methylation of CpG islands in the promoter region is an important avenue for inactivation of p16. The mechanism of methylation of the p16 promoter region, however, has not been elucidated. Recent reports investigating p16 methylation in non-small cell lung cancer (NSCLC) suggest that carcinogens in tobacco smoke induce the DNA methylation process. We investigated the association between methylation of the p16 promoter region and exposure to tobacco smoke in 185 primary NSCLCS: We also studied the relationship of p16 methylation with mutation of the K-ras and p53 genes, as well as with methylation at the DAP-kinase and p14(ARF) loci. Finally, we evaluated the prognostic significance of p16 methylation in NSCLC. The prevalence of p16 methylation was greater in squamous cell carcinoma (41%) compared with adenocarcinoma (22%; P = 0.03; Fisher's exact test). Methylation of p16 was significantly associated with pack-years smoked (P = 0.007; Wilcoxon rank sum test), duration of smoking (P = 0.0009; Wilcoxon rank sum test), and negatively with the time since quitting smoking (P = 0.03; Wilcoxon rank sum test). No methylation of the nearby p14(ARF) locus was detected, and methylation of the DAP-kinase locus was not associated with either p16 methylation or with exposure to tobacco smoke. In patients with stage 1 adenocarcinoma, p16 methylation was an independent risk factor predicting significantly shorter postsurgery survival (P = 0.03), controlling for the significant effects of other factors, including K-ras mutation. These findings suggest that methylation of CpG islands in tobacco-associated cancers occurs in a gene- and tissue-specific manner and is induced directly or indirectly by exposure to tobacco smoke in NSCLC.     

Hypermethylation of the p14(ARF) gene in ulcerative colitis-associated colorectal carcinogenesis

The p14(ARF) protein directly inhibits the MDM-2 oncoprotein, which mediates degradation of the p53 protein. It has been shown that p14(ARF) expression is frequently down-regulated by p14(ARF) gene hypermethylation in colorectal cancer. To determine whether p14(ARF) inactivation was involved in ulcerative colitis (UC)-associated carcinogenesis, the frequency and timing of p14(ARF) methylation was investigated in four different histological stages of UC-associated carcinogenesis. Methylation-specific PCR and bisulfite sequencing were used to determine the prevalence of p14(ARF) gene methylation. p14(ARF) methylation was observed in 19 of 38 (50%) adenocarcinomas, 4 of 12 (33%) dysplasias, and 3 of the 5 (60%) nonneoplastic UC mucosae. In contrast, 3 of 40 (3.7%) normal tissues showed p14(ARF) methylation (chi(2) test: P = 0.0003). Bisulfite sequencing was used to analyze 28 CpGs of p14(ARF) gene in 20 samples. The number of methylated CpGs ranged from 0 to 4, 0 to 20, and 0 to 28 in the normal, dysplastic, and carcinomatous samples, respectively (Kruskall-Wallis test: P = 0.0005). Densely methylated alleles were detected only in carcinomas by bisulfite sequencing. In conclusion, our data suggest that methylation of p14(ARF) is a relatively common early event in UC-associated carcinogenesis. p14(ARF) offers potential as a biomarker for the early detection of cancer or dysplasia in UC. Finally, analyses of p14(ARF) methylation in other organs should explore not only frank cancers but other premalignant lesions.     

Alterations of p14ARF, p53, and p73 genes involved in the E2F-1-mediated apoptotic pathways in non-small cell lung carcinoma.

Overexpression of E2F-1 induces apoptosis by both a p14ARF-p53- and a p73-mediated pathway. p14ARF is the alternate tumor suppressor product of the INK4a/ARF locus that is inactivated frequently in lung carcinogenesis. Because p14ARF stabilizes p53, it has been proposed that the loss of p14ARF is functionally equivalent to a p53 mutation. We have tested this hypothesis by examining the genomic status of the unique exon 1beta of p14ARF in 53 human cell lines and 86 primary non-small cell lung carcinomas and correlated this with previously characterized alterations of p53. Homozygous deletions of p14ARF were detected in 12 of 53 (23%) cell lines and 16 of 86 (19%) primary tumors. A single cell line, but no primary tumors, harbored an intragenic mutation. The deletion of p14ARF was inversely correlated with the loss of p53 in the majority of cell lines (P = 0.02), but this relationship was not maintained among primary tumors (P = 0.5). E2F-1 can also induce p73 via a p53-independent apoptotic pathway. Although we did not observe inactivation of p73 by either mutation or DNA methylation, haploinsufficiency of p73 correlated positively with either p14ARF or p53 mutation or both (P = 0.01) in primary non-small cell lung carcinomas. These data are consistent with the current model of p14ARF and p53 interaction as a complex network rather than a simple linear pathway and indicate a possible role for an E2F-1-mediated failsafe, p53-independent, apoptotic pathway involving p73 in human lung carcinogenesis.     

Aberrant p16 promoter methylation in smokers and former smokers with nonsmall cell lung cancer

Hypermethylation of cytosines in CpG-rich islands of the promoter regions of regulatory genes has been discovered as a common mechanism of gene silencing during carcinogenesis. We analysed 64 primary lung carcinomas for promoter methylation of the tumour suppressor genes (TSGs) p16 (p16(INK4a)/CDKN2A) and p14 (p14(ARF)) by methylation-specific PCR, in order to evaluate aberrant methylation as a potential biomarker for epigenetic alterations in tobacco-related lung cancer. Methylation of p16 was observed in 34% (22/64) of the lung tumours examined. In particular, p16 methylation occurred in nonsmall cell lung cancer (NSCLC) only, with 41 % (22/54) of the tumours being positive. The highest frequency was found in large cell carcinoma (5/7, 71%), followed by adenocarcinoma (9/25, 36%) and squamous cell carcinoma (7/21, 33%). Methylation of the p14 gene was less frequent in lung cancer (4/52, 8%). When association with tobacco smoking was analysed, 42% (21/50) of NSCLC from ever smokers exhibited p16 methylation. Interestingly, the analysis revealed a significantly higher risk of p16 methylation in former smokers as compared to current smokers [odds ratio (OR) 5.1; 95% confidence interval (CI) 1.3-22]. The difference was retained after adjustment for age (OR 3.7; 95% CI 0.9-17). The promoter methylation results were then combined with data on genetic alterations determined previously in the same set of tumours. This data similarly showed that p16 methylation in parallel with p53 gene mutation or p14 methylation occurred more frequently in former smokers than in current smokers (44% vs. 14%; P = 0.035). Taken together, our data suggest that analysis of promoter methylation in TSGs may provide a valuable biomarker for identification of groups with an elevated risk of cancer, such as smokers and ex-smokers.     

Loss of heterozygosity of the Mutated in Colorectal Cancer gene is not associated with promoter methylation in non-small cell lung cancer

'Mutated in Colorectal Cancer' (MCC) is emerging as a multifunctional protein that affects several cellular processes and pathways. Although the MCC gene is rarely mutated in colorectal cancer, it is frequently silenced through promoter methylation. Previous studies have reported loss of heterozygosity (LOH) of the closely linked MCC and APC loci in both colorectal and lung cancers. APC promoter methylation is a marker of poor survival in non-small cell lung cancer (NSCLC). However, MCC methylation has not been previously studied in lung cancer. Therefore, we wanted to determine if MCC is silenced through promoter methylation in lung cancer and whether this methylation is associated with LOH of the MCC locus or methylation of the APC gene. Three polymorphic markers for the APC/MCC locus were analysed for LOH in 64 NSCLC specimens and matching normal tissues. Promoter methylation of both genes was determined using methylation specific PCR in primary tumours. LOH of the three markers was found in 41-49% of the specimens. LOH within the MCC locus was less common in adenocarcinoma (ADC) (29%) than in squamous cell carcinoma (SCC) (72%; P=0.006) or large cell carcinoma (LCC) (75%; P=0.014). However, this LOH was not accompanied by MCC promoter methylation, which was found in only two cancers (3%). In contrast, 39% of the specimens showed APC methylation, which was more common in ADC (58%) than in SCC (13%). Western blotting revealed that MCC was expressed in a subset of lung tissue specimens but there was marked variation between patients rather than between cancer and matching non-cancer tissue specimens. In conclusion, we have shown that promoter methylation of the APC gene does not extend to the neighbouring MCC gene in lung cancer, but LOH is found at both loci. The variable levels of MCC expression were not associated with promoter methylation and may be regulated through other cellular mechanisms.     

肺鳞癌和腺癌组织E2F-1和c-myc及p14ARF蛋白表达临床病理学意义的探讨

目的:研究E2F-1、c-myc和p14ARF蛋白在肺鳞癌及腺癌中的表达情况,探讨其在肺癌发生发展中的作用机制及其与临床病理学特征间的关系。方法:应用免疫组化二步法检测71例肺鳞癌、腺癌及相应癌旁组织中E2F-1、c-myc和p14ARF蛋白的表达情况。结果:肺鳞癌及腺癌组织中E2F-1和c-myc蛋白的阳性表达率分别为83.1%(59/71)和81.7%(58/71),高于癌旁组织中的8.5%(6/71),P<0.05。p14ARF蛋白的阳性表达率为52.1%(37/71),低于相应癌旁组织的74.6%(53/71),P<0.05。并与患者年龄、性别、肿瘤大小、组织分化、病理分型、有无淋巴结转移及TNM分期无关,P>0.05。E2F-1、c-myc和p14ARF蛋白表达经相关分析显示两两相关,P<0.05。结论:肺鳞癌及腺癌内可见E2F-1和c-myc蛋白的过表达及p14ARF蛋白的表达缺失,可能与癌的发生发展有关。