Germline mutation analysis of hPMS2 gene in Chinese families with hereditary nonpolyposis colorectal cancer

AIM: To study the germline mutation of hPMS2 gene in 26 unrelated Chinese hereditary nonpolyposis colorectal cancer (HNPCC) probands and to fulfill the screening strategy for HNPCC in Chinese. METHODS: Genomic DNA was extracted from the peripheral blood. To avoid the interference of pseudogene in detection of the remaining 11 exons (exon 1-5, 9, 11-15), long-range polymerase chain reaction (PCR) was conducted to amplify the complete coding region of hPMS2 gene firstly. Then 1/8 of the PCR productswere used as template to amplify the individual exon respectively and DNA sequencing was done. Direct DNA sequencing of the conventional PCR products of exon 6, 7, 8 and 10 of hPMS2 gene was performed. The same analysis was made in 130 healthy persons without family histories of HNPCC to further investigate the pathological effects of the detected missense mutation. RESULTS: One HNPCC proband fulf illed Bethesda guidelines and was found to carry the germline mutation of hPMS2 gene, which has not been reported in Chinese HNPCC families. It was a missense mutation at c.1532C>T of exon 11. It was detected in three controls as well with an occurrence rate of 2.3% (3/130). Since it could not be found in the PMS2-single nucleotide polymorphism (SNP) database, this missense mutation is a new SNP unreported up to date. Meanwhile, 260 reported SNPs of hPMS2 gene were detected in the 26 HNPCC probands. The 2nd and 5th exons were probably the hot SNP regions of hPMS2 gene in Chinese HNPCC families involving 53.1% of all reported SNP. CONCLUSION: The germline mutation of hPMS2 gene may be rare in Chinese HNPCC families. The 2nd and 5th exons are hot SNP regions of hPMS2 gene.

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

AIM: To descr ibe 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 50patients (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＜0.40＜P＜0.50;coefficient of kurtosis: u = 1.13, 0.20＜P＜0.40, α = 0.20)and AC Ⅱ families (coefficient of skewness: u = 0.63, P＞0.5＞0.20; coefficient of kurtosis: u = 0.84, 0.20＜0.40＜P＜0.50,α = 0.20), but not found in the distribution of the age of diagnosis of the first CRC. When patients with HNPCC-associated cancer suffered from the first malignant tumor in HNPCC families diagnosed by AC Ⅰ and AC Ⅱ, the mean age and median age were 45.1±12.7 years and 44.0 years,45.2±12.7 years and 44.5 years, respectively. The median age of diagnosis of the first tumor of the patients in the later generation was younger than that in the previous generation. Many extracolonic cancers were found to be associated with HNPCC syndrome. Gastric cancer was the most frequent extracolonic cancer followed by endometrial cancer and hepatocarcinoma. In general population of CRC patients, the prevalence of HNPCC diagnosed by AC Ⅰ and AC Ⅱ were 1.3% and 2.2%, respectively.CONCLUSION: The clinical phenotype and prevalence of Chinese HNPCC syndrome are similar to those of Europeans and Americans. Gastric cancer is the most common extracolonic malignant tumor. The age of diagnosis of the first malignant tumor tends to be increasingly younger in patients with HNPCC-related tumors.

Clinical and genetic characteristics of Chinese hereditary nonpolyposis colorectal cancer families

瞄准：到分析，中国世袭 nonpolyposis 的临床的特征渲染表面的癌症(HNPCC ) 家庭并且到屏幕，细菌在职业人员乐队衬里人的失配修理基因 hMLH1 和 hMSH2 的变化。方法：31 个独立中国 HNPCC 家庭在浙江省被收集。所有他们满足了中国 HNPCC 标准。关于耐心的性的临床的数据，颜色的地点表面的癌症，发作的年龄，多重颜色的历史表面的癌症，联系额外的结肠的癌症被记录。PCR 和使中毒的高效液相色谱法(DHPLC ) 被采用屏蔽变化。定序分析被用来发现准确变化地点和显示出反常 DHPLC 侧面的样品的特征。结果：136 个恶意的瘤包括 14 多重癌症在 107 个病人被发现。当， 136 个瘤(77.9%) 中的 106 个被诊断渲染表面的癌症，与在 48.57 +/- 的发作的平均年龄 29.00 年。胃的癌症在这些家庭是最普通的额外的结肠的癌症(10.3%) 。在 hMLHl 和 hMSH2 基因的 23 个不同顺序变化在这 17 个家庭被检测。十五个顺序变化位于前 ons，包括 5 SNP， 3 个沉默变化， 3 个错误感觉变化， 2 个胡说八道变化和 2 框架移动变化。后者七个变化似乎病原。结论：hMLH1 和 hMSH2 基因的 Germline 变化在完成中国 HNPCC 标准的大约三分之一个个 HNPCC 家族被识别。中国 HNPCC 家庭有一些特别临床的特征，例如左边的优势，同步的更少或异时颜色胃的癌症的表面的癌症，和经常的出现。

Role of detection of microsatellite instability in Chinese with hereditary nonpolyposis colorectal cancer or ordinary hereditary colorectal cancer

瞄准：与世袭 nonpolyposis 颜色在病人检测微卫星不稳定性(MSI ) 表面的癌症或平常的世袭颜色表面的癌症并且为与世袭 nonpolyposis 颜色屏蔽家族提供标准在分子的水平的表面的癌症。方法：MSI 与 HNPCC 从 20 个盒子在标本被检测，有平常的世袭颜色的 20 个盒子有分散的颜色的表面的癌症和 20 个盒子借助于聚合酶链反应单人赛的表面的癌症搁浅符合构造多型性。结果：MSI 的积极的率是 85%(17/20 ) 在 HNPCC 组织， 40%(8/20 ) 在平常的世袭颜色，表面的癌症组织并且 10%(2/20 ) 在分散的颜色，表面的癌症分别地组织。差别是重要的。三个组的吝啬的年龄分别地是 43.6， 52.2，和 61.8 年，它逐渐地增加了。正确的半结肠癌的发生分别地是 64.7% ， 37.5% ，和 0% ，它逐渐地减少了并且有有效差量。BAT26 和 BAT25 的表示比率分别地是 94.1% ，它在地点学习了的 5 基因是最高的。糟糕区分的腺癌的发生在在高频率之中的 HNPCC 组是 70.6% 分别地有 50% 和 50% 的微卫星不稳定性(MSI-H ) 比另外的二个组高，。结论：MSI-H 的发生在 HNPCC 组是更高的。MSI 的察觉简单、节俭并且与 HNPCC 和罐头的临床病理特征有高关联被用作一个屏蔽方法检测失配修理基因的细菌线变化。

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.

Clinical and genetic features of International Collaborative Group-hereditary nonpolyposis colorectal cancer families and suspected hereditary nonpolyposis colorectal cancer families

Background Hereditary nonpolyposis colorectal cancer (HNPPC) is one of the most common genetic syndrome related with mutation of human mismatch repair genes. This study was to evaluate the clinical significance of suspected hereditary nonpolyposis colorectal cancer (sHNPCC) criteria I and the clinical and genetic features of International Collaborative Group-HNPCC (ICG-HNPCC) and sHNPCC families Methods Twenty-nine ICG-HNPCC families fulfilling the Amsterdam criteria and 34 sHNPCC families fulfilling the sHNPCC criteria I were collected PCR-SSCP and DNA sequencing analysis were employed to screen the germline mutations of the hMLH1 and hMSH2 genes in these families Results The ICG group had more colorectal cancer (CRC) patients per family than did the suspected group ( P <0 05) No statistical difference was observed in Lynch classification and familial tumor spectrum In both groups of families, colorectal cancer was the most frequent malignancy, and carcinomas of the stomach, pancreas and uterus were the three most common extracolonic malignancies Mutation screening showed that ICG-HNPCC and sHNPCC families had a similar mutation rate (31 0% vs 29 4%, P >0 05), mutation type, and mutation distribution Comparison of the families with and without mutation showed no significant difference in CRC patients per family, Lynch classification, and tumor spectrum Conclusions ICG-HNPCC and sHNPCC families that have similar clinical manifestations and genetic basis indicate a similar nature for cancer development The application of sHNPCC criteria I will facilitate clinical diagnosis and treatment of small

Clinical features and hMSH2/hMLH1 germ-line mutations in Chinese patients with hereditary nonpolyposis colorectal cancer

背景包括 hMSH2， hMLH1， hPMS， hPMS2，和 hMSH6/GTBP，至少五失配修理(MMR ) 基因与世袭 nonpolyposis colorectal 癌症(HNPCC ) 被联系。有 HNPCC 的超过 90% 家庭怀有 hMSH2 和 hMLH1 基因变化。我们在中国病人之中分析了 HNPCC 的临床的特征并且报导在 hMSH2 和 hMLH1 genes.Methods 为变化屏蔽的结果有关性的数据， colorectal 癌症( CRC )的地点，在诊断的年龄，历史同步或 metachronous colorectal 癌症， extracolonic 癌症的例子，并且为从有 HNPCC 的 28 个独立家庭的 126 个病人的肿瘤的组织病理学说被收集。十五个家庭遇见了阿姆斯特丹我标准，并且 13 为诊断满足了日本临床的标准。Genomic DNA 从外部淋巴细胞被提取。聚合酶链反应(PCR ) 和使中毒的高效的液体层析(DHPLC ) 被用来屏蔽 hMSH2 和 hMLH1 基因的编码区域。显示出反常 DHPLC 侧面的样品是 170 个恶意的瘤在 126 个病人， 23 有多重癌症被发现的 sequenced.Results。98 个病人(77.8%) 有 colorectal 癌症，与在 45.9 年和右边的优势的发作的平均年龄。八个 hMSH2 或 hMLH1 基因顺序变化在 12 个家庭，和在 hMSH2 的第三 exon 的胡说八道变化被发现的细菌线 G204X 被发现，代表在曾经在中国蒙古的 ethnicity.Conclusions HNPCC 的人发现的 MMR 基因的第一个变化是典型正染色体地主导的世袭疾病，由早发作描绘了，近似 colorectal 癌症的优势，并且多重同步并且 metachronous colorectal 癌症。DHPLC 是为在 hMSH2 和 hMLH1 基因检测变化的一个强大的工具。在 hMLH1 基因的开始的九 exons 的变化在中国病人是更普通的。

Intraductal papillary mucinous neoplasm of the ileal heterotopic pancreas in a patient with hereditary non-polyposis colorectal cancer: A case report

We report a case of intraductal papillary mucinous neoplasm(IPMN) originating from the ileal heterotopic pancreas in a patient with hereditary non-polyposis colorectal cancer(HNPCC). A 49-year-old woman had a past history of total colectomy and total hysterectomy with bilateral salpingo-oophorectomy due to colonic adenocarcinoma and endometrial adenocarcinoma 11 years ago. Her parents died from colonic adenocarcinoma and her sister died from colonic adenocarcinoma and endometrial adenocarcinoma. The clinician found an ileal mass with necrotic change and the mass increased in size from 1.7 cm to 2.2 cm during the past 2 years on computed tomography. It was surgically resected. Microscopically, the ileal mass showed heterotopic pancreas with IPMN high grade dysplasia. Immunohistochemical staining revealed positive reactivity for MLH1/PMS2 and negative reactivity for MSH2/MSH6. This is the first report of IPMN originating from the ileal heterotopic pancreas in a patient with HNPCC in the English literature.

Clinical characteristics of patients in their forties who underwent surgical resection for colorectal cancer in Korea

BACKGROUND The proportion of young patients with colorectal cancer(CRC),especially in their 40s,is increasing worldwide.AIM To confirm the clinical characteristics of such patients,we planned a study comparing them to patients in their 30s and 50s.METHODS Patients undergoing primary resection for CRC,patients in their 30s,40s and 50s were included in the study.Patient and tumor characteristics,and perioperative and oncologic outcomes were compared.RESULTS Most clinical characteristics of 451(10.5%)patients in their 40s were more similar to those of patients in their 30s than those in their 50s.On pathology data,there were more metastatic lesions(30s vs 40s vs 50s;17.5%vs 21.1%vs 14.9%,P=0.012)in patients in their 40s.There was a trend toward less frequent K-ras mutations among patients in their 40s(48.5%vs 33.3%vs 44.5%,P=0.064).The proportion of patients receiving postoperative chemotherapy was also significantly greater among patients in their 40s(58.3%vs 63.9%vs 56.3%,P=0.032).Five-year overall survival(OS)and disease-free survival(DFS)did not differ between the three groups(5-year OS,92.2%vs 89.8%vs 92.2%,P=0.804;5-year total DFS,98.6%vs 95.7%vs 96.1%,P=0.754;5-year local DFS,98.6%vs 94.3%vs 94.9%,P=0.579;5-year systemic DFS,86.4%vs 87.9%vs 86.4%,P=0.908).CONCLUSION Patients with CRC in their 40s showed significantly more numerous metastatic lesions.The oncologic outcome of stage 1-3 patients in their 40s was not inferior compared to that of those in their 30s and 50s.

Dual primary gastric and colorectal cancer:The known hereditary causes and underlying mechanisms

In this editorial,I commented on the paper by Lin et al,published in this issue of the World Journal of Gastrointestinal Oncology.The work aimed at analysing the clinicopathologic characteristics and prognosis of synchronous and metachronous cancers in patients with dual primary gastric and colorectal cancer(CRC).The authors concluded the necessity for regular surveillance for metachronous cancer during postoperative follow-up and reported the prognosis is influenced by the gastric cancer(GC)stage rather than the CRC stage.Although surveillance was recommended in the conclusion,the authors did not explore this area in their study and did not include tests used for such surveillance.This editorial focuses on the most characterized gastrointestinal cancer susceptibility syndromes concerning dual gastric and CRCs.These include hereditary diffuse GC,familial adenomatous polyposis,hereditary nonpolyposis colon cancer,Lynch syndrome,and three major hamartomatous polyposis syndromes associated with CRC and GC,namely Peutz-Jeghers syndrome,juvenile polyposis syndrome,and PTEN hamartoma syndrome.Careful assessment of these syndromes/conditions,including inheritance,risk of gastric and colorectal or other cancer development,genetic mutations and recommended genetic investigations,is crucial for optimum management of these patients.

林奇综合征相关结直肠癌患者一级亲属癌症筛查行为的影响因素研究

目的 旨在调查林奇综合征相关结直肠癌患者一级亲属的大肠癌相关知识、健康信念和癌症筛查行为现状,并探讨基于健康信念模型的癌症筛查行为预测因素.方法 采用横断面调查法,选取2017年12月至2019年12月广州市1所三级甲等医院结直肠科96例林奇综合征相关结直肠癌患者的265名一级亲属.采用一般资料问卷、结直肠癌知识问卷(Colorectal Cancer Knowledge Questionnaire)、Champion's健康信念量表(Champion's Health Belief Model Scale,CHBMS)进行资料收集.采用描述性统计方法、组间比较和二元logistic回归进行资料分析.结果 林奇综合征相关结直肠癌患者一级亲属的大肠癌相关知识得分处于高、中、低水平的分别为160名(60.4%)、61名(23.0%)和44(16.6%);健康信念总均分为(121.36±13.02)分.61名(23.0%)研究对象接受过林奇综合征相关癌症筛查.Logistic回归分析结果显示,男性、年长、已婚、先证者为多原发癌症、较高的认知和健康信念水平是筛查行为的预测因素(P<0.05).结论 林奇综合征相关结直肠癌患者的一级亲属中关于癌症和癌症筛查的知识和健康信念亟待提高,而这两方面的知识和信念对于促进癌症筛查行为至关重要.干预措施应侧重于健康教育,并加强健康观念,以改善筛查行为.

中国人遗传性非息肉病性结直肠癌相关肿瘤谱及累计发病风险

目的 :探讨中国人遗传性非息肉病性结直肠癌 (HNPCC)相关肿瘤谱和累计发病风险 ,为制定 HNPCC诊治方案提供依据。方法 :随访 31个 HNPCC家系中 1 6 7例肿瘤患者 ,以 Kaplan- Meier生存曲线法估计各种肿瘤发生比例和累计发病风险。 结果 :1 6 7例 HNPCC相关肿瘤患者的首发肿瘤中 ,结直肠癌 1 35例 (80 .8% ) ,胃癌 1 0例 (6 .0 % ) ,子宫内膜癌 8例(4 .8% ) ,卵巢癌 3例 (1 .8% ) ,膀胱癌、乳腺癌、肺癌和脑胶质瘤各 2例 (分别占 1 .2 % ) ,肝癌、胰腺癌和胆囊癌各 1例 (分别占0 .6 % )。70岁时 ,大肠癌发生累计发病风险为 93.3% ,肠外肿瘤发生累计发病风险为 5 6 .1 %。 结论 :中国人 HNPCC肿瘤谱中 ,胃癌发生率较高 ;4 0～ 6 0岁大肠癌发生风险最大 ,5

中国人HNPCC家系中hMSH2基因新突变及其功能分析

目的:报道1个在中国人遗传性非息肉病性结直肠癌(HNPCC)家系中发现的基因突变,并对其功能进行分析。方法:抽提1组符合Amsterdam标准的HNPCC家系先证者和其他家系成员的基因组DNA,PCR扩增先证者hMLH119个外显子和hMSH216个外显子,利用变性高效液相技术(dHPLC)筛查,对异常峰型利用DNA测序方法检测基因突变。发现先证者hMSH2基因存在错义突变后,对家系中其他成员和50名散发性大肠癌患者和100名正常成年人进行相同位点的检测,以判定是单核苷酸多态性位点(SNP)还是突变。利用5对微卫星标记对该家系中的2例肿瘤进行微卫星不稳定分析,免疫组化检测蛋白表达,利用同源建模方法对发现的突变位点进行功能分析,以研究突变的病理意义。结果:在该家系的2例结肠癌患者中均发现hMSH2基因第13外显子2108位出现CA的错义突变,导致703位Ser变异为Tyr,即C.2108C>A(p.Ser703Tyr),微卫星结果显示2例肿瘤均为微卫星高度不稳定(MSIH),肿瘤免疫组化结果显示hMSH1基因表达正常而hMSH2基因不表达。同源建模发现该位点与目前报道的hMSH2基因突变不同,突变位于第Ⅳ结构域,Ser突变为Tyr后空间位阻增大,影响了蛋白的正常折叠和功能。结论:Ser703Tyr是中国人HNPCC的一个新的病理性突变。

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-癌来源于不同克隆。MSI检测可作为HNPCC的临床初筛方法。

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．

MMR蛋白表达缺失在筛选遗传性非息肉病性大肠癌中的意义

目的:探讨DNA错配修复基因(MMR)蛋白表达缺失在筛选遗传性非息肉病性大肠癌(HNPCC)中的作用及其意义。方法:对收集的166例石蜡包埋的疑似遗传性非息肉病性大肠癌组织进行MMR蛋白免疫组化染色。结果:hMLH1蛋白表达阴性(0分)25例,占15.53%,阳性(1～4分)136例,占84.47%;在右半结肠、左半结肠和直肠表达缺失率分别为26.67%(12/45)、5.13%(2/39)和14.29%(11/77);右半结肠癌hMLH1蛋白的表达缺失明显高于左半结肠癌(P<0.05),但与直肠癌无显著性差别(P>0.05)。hMSH2蛋白表达阴性(0分)35例,占21.08%,阳性(1～4分)126例,占75.9%;在右半、左半结肠和直肠表达缺失率分别为33.33%(15/45)、15.38%(6/39)和18.18%(14/77);右半结肠癌的表达缺失明显高于左半结肠癌(P<0.05)和直肠癌(P<0.01)。结论:MMR蛋白免疫组化染色作为一个简单易行的方法在今后检测和确定遗传性非息肉病性大肠癌中将发挥重要作用。

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。

遗传性非息肉病性结直肠癌的微卫星不稳定研究

目的 探讨国人北方人群HNPCC的微卫星不稳定 (microsatelliteinstability ,MSI)发生情况及其意义。方法 44例患者来源于 3 0个HNPCC (hereditarynonpolyposiscolorectalcancer)家系 ,这些家系主要分布于北方 5省市。所有患者均符合BGl 3 (Bethes dal 3 )HNPCC诊断标准。以荧光标记法检测 44例患者的石蜡包埋组织微卫星稳定性。结果 44例患者中高度微卫星不稳定 (highfrequencymicrosatelliteinstability ,MSI H)为 81.81( 3 6/ 44 ) ,低度微卫星不稳定 (lowfrequencymicrosatelliteinstability ,MSI L)为 6.82 ( 3 / 44 ) ,微卫星稳定 (microsatellitestable ,MSS)为 11.3 ( 5 / 44 ) ;所选择的 5个微卫星位点中Bat2 5和Bat2 62个位点MSI H的表达率较高 ,分别为 10 0 %和 97.2 2 %。符合AmsterdamⅡ和符合BGl 3标准的HNPCC患者的MSI H表达率分别为 85 .2 9%和 81,81% ,仅符合BGl 3标准 ,而不符合AmsterdamII的 10个患者中 ,7个发现MSI H。结论 HNPCC肿瘤的MSI H发生率高 ,MSI检测方法简便、易行 ,可作为错配修复基因种系突变初筛方法 ,Bethesdal

MMR蛋白在云南地区遗传性非息肉病性大肠癌中的表达及意义

目的探讨MLH1、MSH2、PMS2和MSH6蛋白在云南地区遗传性非息肉病性大肠癌(heredi-tary nonpolyposis colorectal cancer,HNPCC)中的表达及意义。方法根据目前国内外通常采用的三个标准在云南地区选择遗传性非息肉病性大肠癌病例13个家系中19例肿瘤组织,应用免疫组织化学方法(I HC)检测MLH1、MSH2、PMS2和MSH6蛋白。结果在这13个家系中,MLH1、MSH2、PMS2和MSH6四种蛋白表达缺失率分别为30.77%、38.46%、23.08%、15.38%,其中2例家系先证者同时存在MLH1和PMS2蛋白表达缺失,2例家系先证者同时存在MSH2和MSH6蛋白表达缺失,四种MMR蛋白总的表达缺失率为84.62%。结论云南地区HNPCC病例存在MLH1、MSH2、PMS2和MSH6四种MMR蛋白不同程度的缺失表达,应用I HC检测MMR蛋白可以作为筛选HNPCC家系的一有效手段。

Lynch综合征患者预防性子宫切除与Lynch综合征相关性子宫内膜癌患者非预防性子宫切除的临床特征及预后研究

目的探究Lynch综合征(LS)患者预防性子宫切除(PH)与LS相关性子宫内膜癌(LS-EC)患者非预防性子宫切除(NPH)的临床特征及预后,为改善LS的预后提供指导。方法选取2014年12月—2016年10月河北医科大学第一医院自愿行PH的LS患者16例为PH组,行NPH的LS-EC患者22例为NPH组。收集患者一般资料、病理组织学评估、基因突变分析及随访结果。结果两组患者确诊LS至手术时间、子宫内膜癌(EC)症状比较,差异有统计学意义(P<0.05)。PH组病理结果显示:10例患者标本中有异常发现,其中5例为EC,3例为弥漫性增生,1例透明细胞癌,1例为局灶性增生;剩余6例患者中,3例内膜增生不活跃,2例有子宫肌瘤,1例子宫内膜萎缩。NPH组病理结果显示:内膜样腺癌19例,黏液性腺癌2例,浆液性腺癌1例。PH组EC患者肿瘤直径小于NPH组(P<0.05);两组患者肿瘤位置、淋巴结转移情况、病理类型、内膜样腺癌病理分级、肌层浸润情况比较,差异无统计学意义(P>0.05)。PH组h MLH1基因突变率高于NPH组(P<0.05);两组h MSH2、h MSH6、h PMS2基因突变率比较,差异无统计学意义(P>0.05)。截至2017-03-01,38例LS患者中,存活27例,死亡11例,PH组患者的生存率高于NPH组(χ~2=4.900,P=0.027)。结论 LS患者多伴有肿瘤病史,并且从确诊至手术时间较长,而PH可改善LS患者的预后。