国人HNPCC临床病理及错配修复基因突变特点

目的检测和分析中国人遗传性非息肉性大肠癌(hereditary non-polyposis colorectal cancer, HNPCC)hMSH2和hMLH1基因突变和临床病理特点,并探索高效的检测方法。方法收集31个国人HNPCC家系,采用PCR及变性高效液相色谱分忻(DHPLC)筛查hMSH2和hMLH1基因的突变,对DHPLC图形异常的样本用377DNA测序仪测序。结果31个国人HNPCC家系132个病人中共发现180例恶性肿瘤,其中胃癌19例(10．6％)；同时性癌少见,仅占所有结直肠癌(colorectal cancer,CRC)的3．0％。8个家系携带hMSH2或hMLH1基因序列改变,其中包括第一个带有hMSH2基因突变的蒙古族家系。结论国人中胃痛是发病率仪次于CRC的HNPCC相关肿瘤；DHPLC是一种非常有效的筛选hMSH2和hMLH1基因突变的方法；在中国hMLH1基因尤其是其前9个外显子的突变较hMSH2基因的突变更为常见。     

多重连接依赖的探针扩增技术检测中国人遗传性非息肉病性结直肠癌错配修复基因大片段缺失

目的了解中国人遗传性非息肉病性结直肠癌(HNPCC)家系hMSH2和hMLH1基因大片段缺失特点。方法采用多重连接依赖的探针扩增(MLPA)技术和GeneMapper分析技术检测17个HNPCC家系先证者hMSH2和hM-LH1基因种系大片段缺失。结果在3个家系中分别发现hMSH2基因第8外显子、1~6外显子和1~7外显子3种大片段缺失类型,未发现hMLH1基因大片段缺失。大片段缺失占hMSH2和hMLH1基因总种系病理性突变的19%。结论中国人HNPCC错配修复(MMR)基因大片段缺失发生率较高,hMSH2基因缺失可能更为常见。在分子遗传学检测中有必要开展MMR基因大片段缺失的检测。     

遗传性非息肉病性结直肠癌患者hMLH1和hMSH2基因的突变规律

目的 探讨中国人遗传性非息肉病性结直肠癌(HNPCC)患者hMLH1与hMSH2基因的突变特点.方法 对76个HNPCC家系先证者的DNA样本用PCR法扩增其hMLH1与hMSH2基因的35个外显子,再进行测序以确定突变类型.结果 (1)25个样本发现hMLH1或hMSH2基因突变,总突变率为33%(25/76);(2)检测到的22种突变中:hMLH1基因突变16个,hMSH2基因突变6个;(3)突变类型包括移码突变、无义突变、剪接区突变、错义突变,其中错义突变较多见(hMLH1基因错义突变11个、hMSH2基因5个).结论 中国人HNPCC家系hMLH1和hMSH2突变谱广泛,突变类型多样,hMLH1突变较hMSH2突变多见.     

Novel hMLH1 and hMSH2 germline mutations in African Americans with colorectal cancer.

CONTEXT: Germline mutations of the DNA mismatch repair (MMR) genes hMLH1 and hMSH2 have been shown to cosegregate with the colorectal cancer phenotype in multiple hereditary nonpolyposis colorectal cancer (HNPCC) pedigrees. However, the frequency of these mutations among African American patients with colorectal cancer is unknown. OBJECTIVE: To investigate the frequency of germline alterations of the DNA MMR genes hMLH1 and hMSH2 among African Americans affected by HNPCC and early-age onset colorectal cancer. DESIGN, SETTING, AND PATIENTS: Forty unrelated African American HNPCC and early-age onset colorectal cancer patients (8 women, 3 men) were identified from the cancer registry at a National Cancer Institute-designated referral center, 11 of whom were available for and agreed to study participation from January 1997 to February 1998. The mean age of the subjects was 44 years. An additional 50 age- and sex-matched African Americans without personal or family history of colorectal, endometrial, ovarian, urinary tract, or upper gastrointestinal tract malignancy were also studied as a polymorphism control population. In all subjects, genomic DNA was amplified by polymerase chain reaction for all hMLH1 and hMSH2 exons and screened using single-strand conformation polymorphism (SSCP) analysis. Samples demonstrating significant SSCP shifts underwent automated nucleotide sequencing analysis. MAIN OUTCOME MEASURE: Frequency of hMLH1 and hMSH2 germline alterations in the affected and control subjects. RESULTS: Germline hMLH1 and hMSH2 mutations were detected in 3 (27%) of the African American colorectal cancer probands studied. Each mutation was novel. Two hMLH1 (an A-->T transversion at codon 26 and a GG-->AT substitution across codons 177 and 178) mutations and 1 hMSH2 mutation (a C-->T transition at codon 389) were identified in 3 female study subjects. Six other hMLH1 and hMSH2 alterations were detected but were presumed to be polymorphisms. Neither missense mutation (at codons 26 and 389) was detected in the control population. CONCLUSIONS: The results of our analysis support an association between the 3 mutations reported and predisposition to colorectal cancer. Further studies are needed to define DNA MMR gene-associated colorectal cancer in African Americans, an understudied population at increased risk of fatal colorectal cancer.     

无hMLH1/hMSH2生殖系突变的遗传性非息肉病性结直肠癌3家系报道

目的:考察遗传性非息肉病性结直肠癌(HNPCC)家系hMLH1/hMSH2生殖系突变的情况.方法:选择13个符合Amsterdam标准的HNPCC家系中的先证者,利用DNA 测序检测hMLH1/hMSH2基因突变情况.对其中不携带hMLH1/hMSH2生殖系突变的HNPCC 家系,利用免疫组化检测hMLH1/hMSH2基因表达、PCR-SSCP检测先证者肿瘤组织的微卫星不稳定性(MSI).结果:13个HNPCC家系的先证者中有3例检测不到hMLH1/hMSH2的生殖系突变.3例无hMLH1/hMSH2突变的先证者中,肿瘤组织的微卫星不稳定检测均为MSI-H,免疫组化检测hMLH1/hMSH2基因表达正常.结论:3个严格符合Amsterdam标准的HNPCC家系中未发现hMLH1/hMSH2基因系突变,提示可能存在其他基因突变导致该3个家系HNPCC肿瘤发生.     

可疑遗传性非息肉病性结直肠癌的hMLH1和hMSH2基因突变研究

目的比较分析符合国际诊断标准的遗传性非息肉病性结直肠癌（ＩＣＧＨＮＰＣＣ）家系和提出的可疑ＨＮＰＣＣ家系的分子特征的异同,建立可疑ＨＮＰＣＣ诊断标准并评价其应用价值。方法根据ＡｍｓｔｅｒｄａｍＨＮＰＣＣ诊断标准和作者提出的可疑ＨＮＰＣＣ诊断标准,分别收集得到２９个ＩＣＧ家系和３４个可疑家系。提取先证者的外周血基因组ＤＮＡ,应用ＰＣＲＳＳＣＰ和ＤＮＡ测序的方法进行ｈＭＬＨ１和ｈＭＳＨ２基因的突变筛选。结果２９个ＩＣＧ家系中有９个家系被检出含有ｈＭＬＨ１基因的种系突变,突变率为３１０％;３４个可疑家系中有１０个家系被检出含有ｈＭＬＨ１或ｈＭＳＨ２基因的突变,两个基因的突变率分别为２３５％和５９％。ＩＣＧ组和可疑组中两个基因总突变率之间差异无显著意义（Ｐ＞００５）。ｈＭＬＨ１基因同是两组家系中的主要相关基因。两组家系中,突变均较一致地分布于基因的后半部分,突变类型也极为相似,均以导致短缩蛋白的突变最为常见。结论ＩＣＧ组和可疑组在遗传背景上有着相似之处,对ＨＮＰＣＣ诊断标准有一定的临床应用价值,有助于ＨＮＰＣＣ家系的临床诊断。     

Hereditary non-polyposis colorectal cancer (HNPCC): new germline mutation (190-191 del AA) in the human MLH1 gene and review of clinical guidelines for surveillance of affected families

Hereditary non-polyposis colorectal cancer (HNPCC) is one of the most common genetic diseases comprising at least 5-6% of all colorectal cancers. It is characterized by early onset and mostly right-sided tumors (proximal to the splenic flexure). Molecular analyses are useful methods for diagnosis in index patients and for the detection of risk persons in affected families. A 37-year-old female patient whose family history fulfilled the criteria for hereditary non-polyposis colorectal cancer (HNPCC) was studied using PCR and DNA sequencing for the detection of mutations in the mismatch repair genes hMSH2 and hMLH1. Additionally, literature was reviewed (MEDLINE research until 2000) concerning clinical guidelines for surveillance in HNPCC families. A new deletion of two adenosine nucleotides (190-191 del AA) at codon 64 in exon 2 of the hMLH1 gene was found. The frameshift led to a stop codon at amino acid position 75. This mutation is considered to be disease causing in the development of the colorectal cancer of this family. Six publications with detailed recommendations for the surveillance of risk persons were found in the literature. Following their guidelines, colonoscopy is recommended from 20-30 years on for members of a family who fulfills either the Amsterdam criteria or the Bethesda criteria in combination with a detection of microsatellite instability. Female risk persons should be investigated gynecologically, including a transvaginal ultrasound examination, from 25-35 years on for the early detection of endometrial or ovarian cancer. Recommendations for gastroscopy, abdominal ultrasound examination and urine analysis are not given in all publications. Genetic counseling is recommended from 18 years on for all members of affected families.     

青年大肠癌微卫星不稳定和hMLH1/hMSH2表达缺失在遗传性非息肉病性大肠癌初筛中的应用

目的 探讨青年大肠癌中微卫星不稳定发生率和hMLH1/hMSH2表达缺失率及其在遗传性非息肉病性大肠癌初步筛查中的作用.方法 对73例中国南方青年大肠癌患者(年龄≤40岁)进行微卫星不稳定和hMLH1/hMSH2蛋白免疫组化检测.结果 微卫星不稳定性发生率为56.16%,hMLH1和/或hMSH2表达缺失率为49.32%,二者皆随患者发病年龄的降低而迅速增加;二者对阳性病例的检出率相似.结论 中国人青年大肠癌DNA错配修复基因缺陷为频发事件,运用微卫星不稳定分析和hMLH1/hMSH2蛋白免疫组化检测可在青年大肠癌有效地进行HNPCC患者及家系的初步筛查.     

修订Bethseda标准筛选遗传性非息肉病性结直肠癌患者的队列研究

目的研究修订Bethseda标准筛选遗传性非息肉病性结直肠癌（HNPCC）的价值及在结直肠癌中的构成比。方法对2004年8月至2005年12月进行手术治疗的连续110例患者建立队列、多重荧光聚合酶链反应方法检测肿瘤的微卫星不稳定（MSI）状态,对于MSI结直肠癌患者检测hMSH2、hMLH1和hMSH6基因种系突变。结果110例患者中共检出MSI结直肠癌患者23例（20．9％）。在23例MSI结直肠癌患者中,共发现病理性突变7个（30．4％）,占所有结直肠癌6．4％;其中hMSH6基因种系突变3个,hMSH2基因突变3个,hMLH1基因突变1个。结论以修订Bethesda标准,MSI结直肠癌检出率为20．9％,HNPCC检出率6．4％;在中国人错配修复基因种系突变中hMSH2和hMSH6错义突变比较多见。     

Interpretation of genetic test results for hereditary nonpolyposis colorectal cancer: implications for clinical predisposition testing.

CONTEXT: Genetic testing for cancer predisposition is evolving from purely research applications to affecting clinical management. OBJECTIVE: To determine how often genetic test results for hereditary nonpolyposis colorectal cancer (HNPCC) can be definitively interpreted and used to guide clinical management. DESIGN: Case-series study conducted in 1996 to 1998 in which a complete sequence analysis of hMSH2 and hMLH1 coding sequence and flanking intronic regions was performed. Mutations were categorized as protein truncating and missense. In the case of missense alterations, additional analyses were performed in an effort to assess pathogenicity. SETTING AND PARTICIPANTS: Families were identified by self-referral or health care provider referral to a cancer genetics program. Participants and kindreds were classified into 1 of 4 categories: (1) Amsterdam criteria for HNPCC, (2) modified Amsterdam criteria for HNPCC, (3) young age at onset, or (4) HNPCC-variant. In addition, each proband was classified according to the Bethesda guidelines for identification of individuals with HNPCC. MAIN OUTCOME MEASURE: Alterations of hMSH2 and hMLH1 genes. RESULTS: Twenty-seven alterations of hMSH2 and hMLH1 were found in 24 of 70 families (34.3%). Of these, deleterious mutations that could be used with confidence in clinical management were identified in 25.7% (18/70) of families. The rates of definitive results for families fulfilling Amsterdam criteria, modified Amsterdam criteria, young age at onset, HNPCC-variant, and Bethesda guidelines were 27 (39.3%), 13 (18.2%), 12 (16.7%), 11 (15.8%), and 21 (30.4%), respectively. The prevalence of missense mutations, genetic heterogeneity of the syndrome, and limited availability of validated functional assays present a challenge in the interpretation of genetic test results of HNPCC families. CONCLUSIONS: The identification of pathogenic mutations in a significant subset of families for whom the results may have marked clinical importance makes genetic testing an important option for HNPCC and HNPCC-like kindreds. However, for the majority of individuals in whom sequence analysis of hMSH2 and hMLH1 does not give a definitive result, intensive follow-up is still warranted.     

遗传性非息肉病性大肠癌临床表型分析

目的 探讨我国遗传性非息肉病性大肠癌（HNPCC）患者的临床表型,为临床辨认HNPCC家系提供依据。方法 选择符合阿姆期特丹Ⅱ和日本的HNPCC标准的34个HNPCC家系为研究对象。研究发病的一般规律：（1）确诊时的年龄和性别;（2）绘出家系图;（3）肿瘤发生的部位（包括肠外癌）;（4）同时多原发结肠癌;（5）异时多原发结肠癌;（6）临床表现。结果 （1）34个家系中,18岁以上的家族成员共612人,确诊HNPCC的患者140例,女性47例,男性93例。（2）34个家系均为常染色体显性遗传。（3）确诊时的中位年龄为45．3岁,50岁以前发病者占62．1％,60岁以前发病者占87．1％;（4）154个原发癌灶中,肠外癌灶31个（20．1％）,其中胃癌占肠外癌的41．9％（13／31）,大肠癌灶123个（79．9％）。116例大肠癌患者中,右半结肠癌占66．4％（77／116）,左半结肠癌占33．6％（39／116）。（5）同时多原发癌5例,其中2例为3次多原发癌,3例为2次多原发癌;异时多原发癌6例（含肠外癌）。结论 本组HNPCC的临床特点为（1）发病年龄比西方患者更年轻;（2）右半结肠癌的比例高;（3）大肠癌的垂直传递特征突出;（4）肠外癌以胃癌比例较大;（5）同时原发癌和异时原发癌较多。     

中国人HNPCC家系的临床特征及M3胆碱能受体基因(A)8区突变检测

目的:分析中国人遗传性非息肉病性大肠癌(HNPCC)家系的临床特征并检测这些家系中M3胆碱能受体基因(A)8区的突变情况.方法:根据2003年4月杭州会议制定的中国人HNPCC家系标准收集HNPCC家系共15个,分析其临床特征;提取先证者的外周血基因组DNA,PCR扩增M3胆碱能受体基因第8外显子中一段长153 bp,包含有微卫星位点(A)8的基因片段,直接进行DNA测序.结果:15个家系共有恶性肿瘤患者55例,其中大肠癌患者41例,平均每个家系发生大肠癌2.73例,73%的大肠癌患者发病年龄<50岁,51%的病灶位于近端结肠,40%发生在直肠肛门,同时和异时多原发大肠癌总发生率为12%,2/3的家系属于Lynch Ⅱ型,共发生肠外恶性肿瘤14例(18个),其中胃癌最常见.15例先证者外周血中无1例检测到M3胆碱能受体基因(A)8区的突变.结论:M3胆碱能受体基因与中国人群中HPNCC的发病可能无密切关系.中国人HNPCC家系标准应在临床工作中推广应用,并进一步验证其合理性和科学性.     

Expression of Cyclooxygenase-2 and Its Relationship with Mismatch Repair and Microsatellite Instability in Hereditary Nonpolyposis Colorectal Cancer

Objective To investigate cyclooxygenase-2 （COX-2） expression and its relationship with mismatch repair （MMR） protein expression and microsatellite instability （MSI） in hereditary nonpolyposis colorectal cancer （HNPCC）. Methods A total of 28 cases of colorectal adenoma and 14 cases of colorectal carcinoma were collected between July 2003 and July 2007 from 33 HNPCC families. Sporadic colorectal adenoma （n=32） and carcinoma patients （n=24） served as controls. With samples of tumor tissues and normal colonic mucosa collected from the patients, the protein expressions of COX-2 and MMR （hMLH1, hMSH2, and hMSH6） were examined with immunohistochemical assay. Frequency of MSI in five standard MSI loci BAT25, BAT26, D2S123, D5S346, and D17S250 were analyzed by means of polymerase chain reaction. Results The rate of COX-2 high-expression was 53.6% （15/28） and 42.9% （6/14） in HNPCC adenoma and carcinoma; 62.5% （20/32） and 91.7% （22/24） in sporadic adenoma and carcinoma, respectively. That rate was lower in HNPCC carcinoma than in sporadic carcinoma （P〈0.05）. MMR-deletion rate and percentage of high-frequency MSI （MSI-H） in HNPCC carcinoma were higher than those in sporadic colorectal carcinoma [both 71.4% （10/14） vs. 12.5% （3/24）, both P〈0.01]. Among the 10 MMR-deficient HNPCC carcinoma patients, COX-2 low-expression was observed in 8 cases （80.0%）, while COX-2 high-expression was observed in all of the 4 MMR-positive HNPCC carcinoma cases （P〈0.05）. In comparison to MMR positive HNPCC carcinoma, HNPCC adenoma, and sporadic carcinoma, COX-2 expression was significantly lower in corresponding MMR-deficient cases （all P〈0.05）. The rates of COX-2 low-expression in HNPCC adenoma, HNPCC carcinoma, and sporadic carcinoma with MSI-H were significantly higher than those in the cases with microsatellite stability （all P〈0.05）. Conclusion COX-2 is expressed at a low level in HNPCC carcinoma, different from the high COX-2 expression in sporadic carcinoma.     

甲基转移酶1表达质粒对结肠癌细胞错配修复基因甲基化及其表达的影响

目的 分析DNA甲基转移酶1(Dnmt1)基因的真核表达质粒对人结肠癌细胞错配修复基因甲基化及其转录水平和微卫星不稳定性(MSI)的影响。方法 分别构建含有人的正义Dnmt1(HMT)和反义Dnmt1(THM)的真核表达质粒,将其转染入结肠癌SW1116细胞,以Western印迹实验分析各组细胞Dnmt1蛋白的表达情况。定量PCR检测hMLH1、hMSH2基因的表达。甲基化特异性PCR分析hMLH1、hMSH2启动子区甲基化情况,银染法研究其对微卫星不稳定性的影响。结果 转染正义Dnmt1质粒的细胞hMLH1、hMSH2的启动子甲基化水平升高,基因mRNA表达降低。转染反义Dnmt1质粒可使细胞中hMSH2启动子呈非甲基化状态,基因表达增强。未发现转染正义和反义Dnmt1基因的SW1116细胞存在MSI的变化。结论 重组Dnmt1表达质粒可通过调控人结肠癌细胞中错配修复基因的甲基化影响基因的表达。     

基因hMSH2、hMLH1与p53突变型在散发性大肠癌患者的表达

目的:探讨错配修复基因hMSH2、hMLH1与p53突变型在散发性大肠癌发生中的作用。方法:用聚合酶链反应和单链DNA多态性分析(PCR-SSCP)对45例散发性大肠癌患者肿瘤组织及正常组织基因hMSH2、hMLH1、p53进行检测。结果:45例散发性大肠癌患者中,发生hMSH2、hMLH1、p53基因突变分别为2、6、22例,分别占4.44%、13.33%和48.89%。hMLH1、hMSH2基因在突变型p53患者中的突变率为27.27%明显高于在p53未发生突变的患者中的突变率8.69%(P<0.05)。结论:一定比例的散发性大肠癌患者中存在MMR基因缺陷,其中hMLH1所起的作用大于hMSH2,散发性大肠癌中MMR基因突变与p53突变密切相关。     

遗传性非息肉病性结直肠癌的分子生物学研究现状

遗传性非息肉病性结直肠癌(HNPCC)不同于散发的结直肠癌,其发病机制至今仍未研究透彻。它的发病基础主要是DNA错配修复基因系统的缺陷,如hMLH1、hMSH2等,不能把复制过程中出现的DNA序列的错误纠正过来,从而引起了肿瘤的发生。另外,它还与微卫星不稳定性有关,如CpG岛的甲基化。转化生长因子β/Smad、Wntβ/-catenin信息通路参与了HNPCC的侵袭和转移过程。     

遗传性非息肉病性结直肠癌中环氧合酶2的表达及与错配修复基因表达和微卫星不稳定的相关性

目的 探讨遗传性非息肉病性结直肠癌(HNPCC)腺瘤及癌组织中环氧合酶2(COX-2)的表达及其与错配修复(MMR)基因蛋白表达、微卫星不稳定(MSI)之间的关系.方法 来源于33个HNPCC家系的大肠腺瘤28例、大肠癌14例,随机留取经病理确诊的32例散发大肠腺瘤和24例散发大肠癌标本作为对照;采用免疫组织化学和PCR技术,检测腺瘤及癌组织中COX-2、MMR基因(hMLH1、hMSH2、hMSH6)蛋白表达及BAT-25、BAT-26、D2S123、D5S346、D17S250 5个微卫星位点的MSI状态.结果 COX-2在HNPCC腺瘤及癌组织中高表达率分别为53.6%(15/28)、42.9%(6/14),在散发大肠腺瘤和大肠癌中高表达率分别为62.5%(20/32)、91.7%(22/24),HNPCC癌组织中的COX-2表达明显低于散发大肠癌(P＜0.05).HNPCC大肠癌中MMR蛋白表达缺失率、高度微卫星不稳定(MSI-H)发生率[均为71.4%(10/14)]明显高于散发大肠癌[均为12.5%(3/24),均P＜0.05].10例MMR蛋白表达缺失的HNPCC大肠癌中,8例为COX-2低表达;4例MMR蛋白表达阳性的HNPCC大肠癌全部为COX-2高表达.在MMR表达缺失的HNPCC大肠癌、HNPCC腺瘤、散发大肠癌中COX-2的表达均显著少于MMR表达阳性者(均P＜0.05).MSI-H的HNPCC大肠癌、HNPCC大肠腺瘤、散发大肠癌中COX-2低表达率分别为80.0%(8/10)、66.7%(12/18)、66.7%(2/3);与微卫星稳定(MSS)组比较差异均有统计学意义(均P＜0.05).结论 与散发性大肠癌相比,COX-2在HNPCC大肠癌组织中表达明显减少;COX-2在大肠腺瘤及癌组织中的表达率与MMR蛋白表达缺失和MSI-H呈明显的负相关;COX-2、MMR蛋白表达、MSI的检测对于进一步研究大肠肿瘤的发病途径及干预治疗具有重要意义.     

胃癌家系人群hMLH1基因点突变的分析

[目的 ]研究我国北方地区胃癌高发人群hMLH1基因突变情况。 [方法 ]取 4个胃癌家系非肿瘤人群 94份和对照人群的 10 0份外周血 ,提取DNA ,聚合酶链反应扩增hMLH1基因的第 8和第 12外显子 ,用毛细管电泳测定外显子的单链构象多态性 ,进而对电泳峰形异常者进行测序。 [结果 ]胃癌家系非肿瘤人群 94例标本中 ,hMLH1基因突变 2 2例 ,突变率 2 3% ,其中第 8外显子突变12例 ,第 12外显子突变 10例 ;10 0例对照标本突变 4例 ,突变率 4 % ,其中第 8外显子突变 2例 ,第12外显子突变 2例。胃癌家系人群hMLH1基因突变率明显高于对照人群 ,且突变的碱基与遗传性非息肉性结肠癌发生突变的碱基位置相同。[结论 ]我国北方地区胃癌高发人群可能有着与HNPCC相似的错配修复基因突变。     

散发性结直肠癌组织中hMSH2和hMLH1的表达及其意义

[摘要] 目的 检测错配修复基因hMSH2和hMLH1在散发性结直肠癌组织和正常结直肠组织中的表达,探讨其在结直肠癌发病过程中的意义。方法 采用免疫组化SP法检测结直肠癌和正常结直肠组织中hMSH2和hMLH1的表达。结果 部分结直肠癌组织中有不同程度的hMSH2 和（或）hMLH1蛋白表达缺失,与正常结直肠组织相比差异有显著性（P<0.05）;hMSH2 和 hMLH1蛋白表达缺失与肿瘤组织的分化程度相关（P<0.05）,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明显关系（P>0.05）。结论 结直肠癌组织中hMSH2和（或）hMLH1的缺失可能与部分散发性结直肠癌的发生相关;hMSH2和hMLH1缺失与肿瘤组织的分化程度相关,提示错配修复功能的缺陷可能导致肿瘤恶性程度的加重。     

遗传性非息肉病性结直肠癌家庭肠外肿瘤病变特点分析

目的　通过分析遗传性非息肉病性结直肠癌 (HNPCC)肠外肿瘤的病变特点来探讨其发病规律。方法　采用Amsterdam标准Ⅱ收集HNPCC家系 ,对收集的 9个家系进行病例查阅、随访和回顾。结果　在 9个家系中 ,有 2 1例肠外肿瘤发生 ,4例为同步肿瘤 ,1 7例为异步性肿瘤。常见的为胃癌和子宫内膜癌。结论　大肠外肿瘤是HNPCC家系的重要组成部分 ,我国常见的为胃癌和子宫内膜癌。对其家系成员应定期随访监测