遗传性非息肉病性结直肠癌家系临床特征及诊断标准分析

目的 探讨中国人遗传性非息肉病性结直肠癌(HNPCC)家系临床特点和诊断。方法 收集69个HNPCC家系(符合Amsterdam标准Ⅱ33个、Japan标准24个、Bethesda指导原则1～3项12个)，对其进行分组和比较分析。结果 69个家系共有癌症277人，肠癌213人，肠外癌64人。HNPCC癌患者中位年龄为46岁。发病高峰年龄为40～49岁。共有两代以上垂直传递家系65个，占所有家系的94．2％。肠癌患者中(右)半结直肠癌占62％。共有多原发癌33例，占癌患者的11．9％。共有肠外癌64人，占癌患者的23．1％，其中胃癌、子宫内膜癌分别占癌患者的6．5％和4％，列前两位。结论 HNPCC家系与SCRC相比具有发病年龄轻、垂直传递、肠外癌发病率高、肿瘤谱广、常见多原发癌、好发于右半结直肠的特点。某些特点与两方国家不完全相同。     

遗传性非息肉病性结直肠癌的临床特征与诊断原则

目的：探讨遗传性非息肉病性结直肠癌（HNPCC）的临床特点和诊断。方法：收集22个符合Amsterdam标准的HNPCC家族，分析其临床特点。结果：本组符合Amsterdam标准的HNPCC发病率为2．6％＜22个家族有恶性肿瘤患者101例，结直肠癌患者84例，发生第一个结直肠癌的平均年龄为45．7岁，位于脾曲近侧结肠和直肠的分别占58．3％和23．8％。23．8％患者发生同时或异时多原发结直肠癌。20例患者发生肠外肿瘤，以胃癌居多。结论：HNPCC具有发病年龄早，近侧结肠多见，同时和异时多原发结直肠癌发生率高的特点，诊断治疗及随访应有别于散发性结直肠癌。本组肠外肿瘤以胃癌发生率高，与国外报道不同。建立中国人的HNPCC诊断标准是必要的。     

中国人遗传性非息肉病性结直肠癌常见临床表型特征与肠外肿瘤谱分析

目的系统地探讨中国人遗传性非息肉病性结直肠癌（HNPCC）常见临床表型特点及肠外肿瘤谱。方法在自行收集的HNPCC家系基础上,采用meta分析方法,遴选近年公开发表的有关中国人HNPCC综合征临床表型的文献,扩大样本含量,共收集142个符合Amsterdam标准Ⅰ或Amsterdam标准Ⅱ的HNPCC家系,其中57个家系具有完整资料。结果在符合Amsterdam标准Ⅰ的家系中,发生结直肠癌患者占82．4％（215／261）,发生肠外恶性肿瘤的患者占25．3％（66／261）,仅患肠外恶性肿瘤的患者占17．6％（46／261）,发生多原发恶性肿瘤的患者占19．2％（50／261）,首发恶性肿瘤为结直肠癌者占80．8％（211／261）,其中位于右半结肠者占66．8％（141／211）;在结直肠癌患者中,多原发结直肠癌占19．1％（41／215）,同时发生结直肠癌与肠外恶性肿瘤者占9．3％（20／215）;结直肠外肿瘤谱涉及23种肿瘤,其中胃癌、子宫内膜癌、肝癌、卵巢癌、食管癌、胰腺癌、乳腺癌、甲状腺癌、肺癌、小肠恶性肿瘤最为常见。Amsterdam标准Ⅱ家系中有相似的结果。结论中国人HNPCC常见临床表型特征与西方国家相似;中国人肠外肿瘤谱较广,其中胃癌、子宫内膜癌、卵巢癌、肝癌、食管癌等最为常见。     

遗传性非息肉病性结直肠癌家系临床病理特征分析

目的 探讨中国人遗传性非息肉病性结直肠癌(HNPCC)家系发病特点及预后.方法 收集24个符合Amsterdam标准的HNPCC家系,绘制其家系图谱、收集临床病理及随访资料,分析中国人HNPCC的发病特点及预后.结果 24个HNPCC家系中,共有肿瘤患者116例(其中先证者多原发癌16例,家系成员多原发癌9例),发病年龄19～74岁,其中结直肠癌灶120个,肠外相关肿瘤32个.在24个HNPCC家系的先证者中,患第一结直肠癌的平均年龄为42.5岁,男性多于女性,右半结肠肿瘤多于左半结肠;肿瘤分化均较好,以中分化多见,病理类型以管状腺癌多见,占45.8%(11/24);截至随访结束时,术后生存≥5年者共14例,占58.3%(14/24),其中9例超过10年,最长1例存活时间已达27年.结论 中国人HNPCC以中分化管状腺癌多见,发病年龄较轻,右半结肠癌多见.     

遗传性非息肉性结直肠癌患者腺瘤和癌组织微卫星基因型分析

背景：遗传性非息肉性结直肠癌（HNPCC）是一种由错配修复基因种系突变引起的常染色体显性遗传病，高度微卫星不稳定（MSI—H）为其分子生物学特征之一。目的：利用5个微卫星位点建立正常结直肠黏膜、结直肠腺瘤和癌组织的微卫星基因型，探讨HNPCC的MSI发生情况和MSI检测的临床意义。方法：纳入源自33个HNPCC家系的腺瘤28例和腺癌14例，其中4例为同步腺瘤-癌；以32例散发性结直肠腺瘤和24例散发性结直肠癌作为对照。选用BAT25、BAT26、D2S123、D5S346、D17S250五个微卫星位点行荧光标记聚合酶链反应（PCR），以GeneMapper软件分析PCR产物。通过与正常黏膜微卫星序列PCR片段长度进行比较，判定腺瘤和癌组织的MSI情况。结果：HNPCC腺瘤和癌组织MSI-H发生率分别显著高于散发性结直肠腺瘤和结直肠癌（64-3％对3．1％，71.4％对12．5％，P〈0．05）。4例同步腺瘤-癌均表现为MSI—H．其腺瘤和癌组织的MSI类型不同。结论：HNPCC腺瘤和癌组织MSI—H发生率高。同步腺瘤一癌来源于不同克隆。MSI检测可作为HNPCC的临床初筛方法。     

新疆地区遗传性非息肉病性大肠癌临床病理特点分析

目的探讨新疆地区遗传性非息肉病性大肠癌（HNPCC）的临床病理特点,并对中国人HNPCC诊断标准进行评价。方法新疆地区符合中国人HNPCC诊断标准的HNPCC 12家系63例（HNPCC组）,其中4家系同时符合AmsterdamⅡ标准为A组,其余为B组;随机选取同期收治的无家族遗传倾向的散发性大肠癌152例（散发组）。采用SPSS16.0软件,对HNPCC组、散发组间及HNPCC中A、B组患者的临床病理资料进行比较。结果 HNPCC组发病年龄〈50岁者23例,肿瘤位于右半结肠39例,低分化癌32例,多发癌12例,肠外恶性肿瘤22例,Dukes A期24例,黏液腺癌31例;散发组分别为26、50、38、6、5、34、43例。两组比较,P均〈0.05。HNPCC中A、B组患者临床病理特征比较,P均〉0.05。结论新疆地区HNPCC的特点是发病年龄早、右半结肠多见、病理分化差、多发癌常见,肠外恶性肿瘤发生率高;与AmsterdamⅡ标准比较,中国人HNPCC诊断标准更适用于新疆地区HNPCC的诊断。     

遗传性非息肉病性结直肠癌血清的蛋白质组学

目的:研究遗传性非息肉病性结直肠癌(HNPCC)与散发性结直肠癌患者术前血清蛋白质的表达差异,以期发现可用于HNPCC诊断的生物学指标.方法:应用表面增强激光解吸电离飞行时间质谱(SELDI-TOF-MS)技术结合蛋白质芯片分别检测20例HNPCC和25例散发性结直肠癌患者术前血清蛋白质组分.将获得的蛋白质谱采用美国C...     

遗传性非息肉病性结直肠癌的遗传及病理分析

遗传性非息肉病性结直肠癌综合征(hereditary nonpol-yposis colorectal cancer,HNPCC)家族人群为结直肠癌最常见的高危因素。依据伴肠外肿瘤与否,该病又分为Lynch Ⅰ型(无肠外肿瘤)和Lynch Ⅱ(伴肠外肿瘤)。由于缺乏明显的可供诊断的临床病理学特点及可监测的生化指标,给早期发现及诊断本病带来困难,1990年,国际HNPCC合作组建立了该病的临床诊断标准——Amsterdam标准,内容为:(1)3个以上亲属患者有病理证实的结直肠癌,其中1人为另2人的一级亲属;(2)连续二代人患结直肠癌;(3)其中至     

遗传性非息肉病性结直肠癌临床分子诊断的研究进展

遗传性非息肉病性结直肠癌(hereditary nonpolyposis colorectal cancer,HNPCC)是一种由于错配修复基因(mismatch repair gene,MMR)突变导致的常染色体显性遗传性疾病,占结直肠癌的5%-15%.研究显示,与HNPCC发生相关的错配修复基因有hMSH2、hMLH1、hMSH6、hPSM1和hPSM2.HNPCC肿瘤具有发病早、近段结肠多见、原发癌多见、肠外肿瘤多见、病理以黏液腺癌为主的特点.到目前为止,HNPCC的诊断主要依赖病史及相关遗传检测结果.对于符合Amsterdam Ⅱ或Bethesda标准的结直肠癌患者应进行微卫星不稳定(microsatellite instability,MSI)和免疫组织化学错配修复蛋白的检测,继而进行错配修复基因等种系突变检测.     

大肠多原发癌临床分析42例

目的：探讨大肠多原发癌及其肠外器官恶性肿瘤的流行病学、临床病理特点及诊治方法．方法：对我院1980-2005年收治的42例大肠多原发癌及其肠外恶性肿瘤的临床、病理及随访资料进行回顾性分析．结果：本组病例占我院同期收治的所有大肠癌的3．10%(42/1354),其中同时性大肠多原发癌13例(0．96%)；异时性大肠多原发癌29例(2．14%)；合并肠外器官恶性肿瘤的有20例(1．48%)．大肠癌灶以右半结肠和直肠为多,肠外癌灶以胃、小肠、乳腺、卵巢、子宫为多；病理均以腺癌为主．共有12例(28．6%)符合遗传性非息肉病性大肠癌(HNPCC)阿姆斯特丹标准Ⅱ,16例(37．2%)符合中国人HNPCC诊断标准．结肠纤维镜检查有助于多原发癌的检出．结论：大肠多原发癌的发病率较高,其流行病学和临床病理特点突出．应注意重视结肠纤维镜检查,术中应仔细全面探查,加强术后随访有助于HNPCC的发现和诊断,以避免误诊漏诊．     

Clinical phenotype and prevalence of hereditary nonpolyposis colorectal cancer syndrome in Chinese population

AIM: To describe systematically the clinical characteristics and phenotype of HNPCC families and the prevalence of HNPCC in the general population of CRC patients in China. METHODS: HNPCC kindreds and CRC patients were from two sources. One was that we consecutively investigated kindreds and patients by ourselves. And the other was the published Chinese and foreign literature related to Chinese HNPCC syndrome. There were 142 HNPCC families fulfilling AC I and/or AC II including 57 families with detailed data, and 3874 general primary CRC patients in all. All statistical tests were two-sided. RESULTS: In AC I families, the number of Lynch syndrome I and II families were 25 (47.2%) and 28 (52.8%) respectively. There were 215 patients (82.4%) with CRC, 67 patients (25.7%) with extracolonic cancer and 50 patients (19.2%) with multiple primary cancers. In all CRC patients, multiple primary CRC were in 41 patients (19.1%), and the first-CRC was right-sided colorectal cancer in 143 patients (66.5%) and rectal cancer in 44 patients (20.5%). 8.8% and 19.2% of the first cancer were CRC and extracolonic cancers. Among those patients whose first cancer was CRC, 66.8% and 19.9% were right-sided colorectal cancer and rectal cancer, respectively. The similar results were found in AC II families. Normal distribution was only found in the distribution of the age of diagnosis of the first cancer in both AC I families (coefficient of skewness: u = 0.81, 0.20<0.400.5> 0.20; coefficient of kurtosis: u = 0.84, 0.20<0.40相似文献   

Clinicopathologic characteristics of Chinese hereditary non‐polyposis colorectal cancer

OBJECTIVE: The aim of the present study was to examine the clinicopathologic characteristics of Chinese patients with hereditary non‐polyposis colorectal cancer (HNPCC) and those with suspected (atypical) HNPCC. METHODS: Personal and family cancer histories were obtained by reviewing the charts and interviewing the proband and participating relatives. Families were identified and classified into three groups by either the Amsterdam or Japanese criteria for HNPCC. Clinical characteristics including onset, localization, stage of colorectal cancer (CRC), tumor multiplicity, survival and mucinous histology were evaluated. RESULTS: Ninety‐eight subjects comprising 92 CRC patients and six extracolonic cancer patients from 13 typical and 19 non‐typical HNPCC kindreds were enrolled. There were 53 patients with CRC, one with both CRC and extracolonic cancer and five with extracolonic cancer in the typical HNPCC group, and in the atypical group there were 38 patients with CRC and one with extracolonic cancer. The average onset age of typical HNPCC and atypical HNPCC was 48 and 50 years, respectively, without statistical difference. There were no statistical differences in sex, pathological type, stage, site distribution of the tumor or survival between typical HNPCC and atypical HNPCC groups. There were 11.1% (6/54) metachronous CRC in the typical HNPCC group, and 7.9% (3/38) metachronous and 2.6% (1/38) synchronous CRC in the atypical HNPCC group. CONCLUSION: The Amsterdam criteria are important, but inappropriate for the establishing the clinical diagnosis of HNPCC in Chinese patients, with some atypical families that did not fulfil all the Amsterdam criteria probably possessing similar clinicopathogical features and genetic alterations. It seems that HNPCC should be considered in some suspected cases.     

Clinical characteristics and diagnosis of patients with hereditary nonpolyposis colorectal cancer

AIM: To study the clinical characteristics of hereditary nonpolyposis colorectal cancer (HNPCC) in the Chinese population and discuss the identification and management of the patients with HNPCC. METHODS: A series of 140 patients with colorectal cancers (CRC) and HNPCC associated tumors from 30 families fulfilling the Amsterdam criteria were analyzed. RESULTS: A total of 118 patients had CRC. Average age at diagnosis of the first CRC was 45.7 years, 56.8 % and 23.4 % of the first CRC were located proximal to the splenic flexure and in the rectum respectively. Twenty-three (19.5 %) had synchronous and metachronous CRC. Twenty-seven patients were found to have extracolonic tumors. Gastric carcinoma was the most common tumor type in our series (44.4 %). CONCLUSION: The frequency of HNPCC was 2.6 % in our series of patients. The main features are an excess of early onset with a propensity to involve the proximal colon, and high frequency of multiple foci. Management and surveillance for these patients should be different from sporadic CRC. Contrary to American and European reports, gastric cancer seems more frequent than endometrial cancer in Chinese. It is necessary to formulate a new HNPCC criterion for Chinese patients.     

Suspected hereditary nonpolyposis colorectal cancer

PURPOSE: The aim of this study was to determine the frequency of mutations in the mismatch repair genes in families suspected of having hereditary nonpolyposis colorectal cancer. METHODS: We devised two criteria for families suspected of having hereditary nonpolyposis colorectal cancer (Criteria I and II). Criteria I consist of at least two first-degree relatives affected with colorectal cancer with at least one of the following: development of multiple colorectal tumors including adenomatous polyp, at least one colorectal cancer case diagnosed before the age of 50, and occurrence of a hereditary nonpolyposis colorectal cancer extracolonic cancer (endometrium, urinary tract, small intestine, stomach, hepatobiliary system, or ovary) in family members. Criteria II consist of one colorectal cancer patient with at least one of the following: early age of onset (<40 years); endometrial, urinary tract, or small intestine cancer in the index patient or a sibling (one aged <50 years); and two siblings with other integral hereditary nonpolyposis colorectal cancer extracolonic cancers (one aged <50 years). A questionnaire was mailed to members of the International Collaborative Group on Hereditary Non-Polyposis Colorectal Cancer to determine the mutation detection rate in mismatch repair genes from the families fulfilling these criteria. For comparison the mutation detection rate for families fulfilling the Amsterdam hereditary nonpolyposis colorectal cancer criteria in each institution was also obtained. RESULTS: Data were obtained from eight different institutions (in 7 different countries). In a total of 123 patients from 123 families (67 families fulfilling Criteria I and 56 families fulfilling Criteria II), genetic testing for germline mismatch repair gene variants was performed. Germline mutations of the hMLH1 or hMSH2 genes were identified in 24 families (20 percent). Of these, the mutation detection rate for families fulfilling Criteria I was 28 percent (19/67). The mutation detection rate for families fulfilling Criteria II was 9 percent (5/56). In these eight institutions, the overall mutation detection rate for families fulfilling the Amsterdam hereditary nonpolyposis colorectal cancer criteria was 50 percent (77/154). CONCLUSION: The Criteria I for suspected hereditary nonpolyposis colorectal cancer have the advantages that they can be applied to nuclear families and they can include extracolonic cancers. The results of this study suggest that families fulfilling Criteria I should be offered genetic testing. The relatively low mutation detection rate in those families fulfilling Criteria II suggests that, using current techniques, genetic testing in these families is not practical.     

MLH1 promoter germline-methylation in selected probands of Chinese hereditary non-polyposis colorectal cancer families

AIM： To detect the MLH1 gene promoter germline- methylation in probands of Chinese hereditary non- polyposis colorectal cancer （HNPCC）, and to evaluate the role of methylation in MLH1 gene promoter and molecular genetics in screening for HNPCC.METHODS： The promoter germline methylation of MLH1 gene was detected by methylation-specific PCR （MSP） in 18 probands from unrelated HNPCC families with high microsatellite-instability （MSI-H） phenotype but without germline mutations in MSH2, MLH1 and MSH6 genes. At the same time, 6 kindreds were col- lected with microsatellite-stability （MSS） phenotype but without germline mutations in MSH2, MIH1 and MSH6 genes as controls. The results of MSP were confirmed by clone sequencing. To ensure the reliability of the results, family H65 with nonsense germline mutation at c.2228C 〉 A in MSH2 gene was used as the negative control and the cell line sw48 was used as the known positive control along with water as the blank control. Immunochemical staining of MIH1 protein was performed with Envision two-step method in those patients with aberrant methylation to judge whether the status of MLH1 gene methylation affects the expression of MLH1 protein.RESULTS： Five probands with MIH1 gene promoter methylation were detected in 18 Chinese HNPCC families with MSI-H phenotype but without germline mutations in MSH2, MLH1 and MSH6 genes. Two of the five probands from families H10 and H29 displayed exhaustive-methylation, fulfilling the Japanese criteria （JC） and the Amsterdam criteria （AC）, respectively. The other 3 probands presented part-methylation fulfilling the AC. Of the 13 probands with unmethylation phenotype, 8 fulfilled the JC and the Bethesda guidelines （BG）, 5 fulfilled the AC. The rate of aberrant methylation in MLH1 gene in the AC group （22.2%, 4/18） was higher than that in the JC/BG groups （5.6%, 1/18） in all HNPCC families with MSI-H phenotype but without germline mutations in PISH2, PIIH1 and MSH6 genes. However, no proband with methy     

Analysis for phenotype of HNPCC in China

AIM：The aims of this study were to identify the clinicopathological features of Chinese HNPCC families and to evaluate the value of criteria for suspected HNPCC(sHNPCC)in clinical diagnosis.METHODS:According to the follow-up records,54HNPCC families(including12ICG-HNPCCfamilies and 42sHNPCC families)were screened out from patients with colorectal cancers(CRCs),operated upon in 2^nd Affiliated Hospital of Zhejiang University from 1984to2001.Cinical data of probands and tumor spectrum in these families were listed and analyzed.RESULTS:(1)Mean age.proportion of colonic cancer,poorly differentiated cancer,multiple CRCs and Dukes‘A+Bof the probands in ICG-HNPCCand sHNPCC kindred were39ys and 47.5ys,75%and 62%,0and 12.8%,16.7%and 14.3%,58.3%and81%,respectively,Compared with sporadic colorectal cancers,probands from ICG-HNPCCand sHNPCC families were obviousy different at age of onset(P=0.025 and 0.031).tumor location(P=0.001and 0.000),differentiation(P=0.002and 0.011)and development of multiple tumors(P=0.014and0.002).(2)A total of 178 malignant neoplasms were found in54HNPCC families.including 139colorectal cancers.Besides of colorectal cancer,extracolonic tu8mors occurred in stomach,endometrium,hepatobiliary system,and so on(8gastric cancers,6endometrial cancers,6hepatobiliary system cancers and 19others)can also be seem in Chinese ICG-HNPCCand sHNPCC families.CONCLUSION:(1) Chinese HNPCC families have specific clinicopathological features,such as early onset,predilection for the invovement of colon,tendency of multiple CRCs,development of extracolonic tumors and well differentiation.(2)The criteria for suspected HNPCCis useful in clinical diagnosis and management of HNPCC.     

Extracolonic cancers associated with hereditary nonpolyposis colorectal cancer in the Utah Population Database

BACKGROUND: The data describing the extracolonic cancers associated with hereditary nonpolyposis colorectal cancer (HNPCC) are variable. METHODS: We ascertained all Amsterdam I criteria-positive pedigrees (N = 18) in the Utah Population Database (UPDB). We identified the extracolonic cancers in the colorectal cancer cases (N = 65) in these pedigrees, and in their first- (N = 509) and second-degree (N = 1,611) relatives. Standardized morbidity ratios were estimated by comparing the observed rates of extracolonic cancer in defined sets of relatives of probands with population expected rates estimated internally from the UPDB. RESULTS: The extracolonic cancers observed in significant excess in the 65 Amsterdam I criteria-positive colorectal cancer (CRC) cases in the UPDB were uterine (N = 3, p = 0.003), lip (N = 2, p = 0.007), stomach (N = 2, p = 0.009), female genitalia (N = 1, p = 0.004) and larynx (N = 1, p = 0.05). Extracolonic cancers observed in significant excess in the 509 first-degree relatives of the 65 colorectal cancer (CRC) cases in these Amsterdam I criteria pedigrees included: thyroid (N = 5, p = 0.0002) and prostate (N = 19, p = 0.002). Thyroid cancer (N = 6, p = 0.003) was found in significant excess in the second-degree relatives of the Amsterdam I criteria-positive CRC cases. CONCLUSIONS: In this population-based examination of the extracolonic cancers at excess in classic HNPCC pedigrees (selected by Amsterdam I criteria) we not only observed many of the same cancers previously reported to be associated with HNPCC in both CRC probands and their relatives, but also identified several previously unreported associations. Although our sample size is small, this study is population based, lacks ascertainment and recall bias, and benefits from uniform, consistent diagnoses of all cancers in a statewide registry.     

Clinical and genetic characteristics of Chinese hereditary nonpolyposis colorectal cancer families

AIM: To analyze the clinical characteristics of Chinese hereditary nonpolyposis colorectal cancer (HNPCC) families and to screen the germline mutations of human mismatch repair genes hMLH1 and hMSH2 in the probands.METHODS: Thirty-one independent Chinese HNPCC families were collected in Zhejiang Province. All of them met Chinese HNPCC criteria. Clinical data about patient gender, site of colorectal cancer, age of onset, history of multiple colorectal cancer, associated extracolonic cancer were recorded. PCR and denaturing high performance liquid chromatography (DHPLC) were employed to screen the mutations. Sequencing analysis was used to find out the exact mutation site and characteristics of the samples showing abnormal DHPLC profiles.RESULTS: One hundred and thirty-six malignant neoplasms were found in 107 patients including 14 multiple cancers. One hundred and six of the 136 neoplasms (77.9%) were diagnosed as colorectal cancer, with an average age of onset at 48.57 ± 29.00 years. Gastric cancer was the most common extracolonic cancer (10.3%) in these families. Twenty-three different sequence variations in hMLH1 and hMSH2 genes were detected in these 17 families. Fifteen sequence variations were located in the exons, including 5 SNPs, 3 silent mutations, 3 missense mutations, 2 nonsense mutations and 2 frameshift mutations. The latter seven mutations seemed to be pathogenic.CONCLUSION: Germline mutations of hMLH1 and hMSH2 genes are identified in about one-third HNPCC kindreds fulfilling Chinese HNPCC criteria. Chinese HNPCC families have some particular clinical characteristics, such as a left-sided predominance, less synchronous or metachronous colorectal cancer, and frequent occurrence of gastric cancer.