微卫星不稳定性：基因研究的新热点

１原文的要点作者应用ＰＣＲ—ＳＳＣＰ技术，对大肠癌切除病例，从病理蜡块材料的回顾性研究中，找到２４例多原发大肠癌及２１例单发大肠癌从蜡块中切下１０余微米厚的癌组织，提取癌细胞中的ＤＮＡ，进行ＰＣＲ扩增后电泳，根据ＤＮＡ带型，与正常的ＤＮＡ条带比较，以寻找条带的移位，数目增多或减少等异常条带，即表示ＤＮＡ重复序列的改变，以此证实为微卫星不稳定性阳性（ＭＳＩ＋）病例．结果表明，多原发大肠癌为ＭＳＩ＋为７１％，单发大肠癌ＭＳＩ＋为３８％．名词解释①微卫星微卫星（ｍｉｃｒｏｓａｔｅｌｌｉｔｅ，ＭＳ）是指…     

17号染色体微卫星不稳定性和杂合性丢失与非小细胞肺癌的关系

目的　明确１７ 号染色体微卫星不稳定性（ＭＩ） 和杂合性丢失（ＬＯＨ） 与非小细胞肺癌（ＮＳＣＬＣ） 的关系。方法　对３５ 例ＮＳＣＬＣ肿瘤切除组织和肿瘤旁正常组织,采用聚合酶链反应微卫星长度多态性分析方法检测了１７ 号染色体上４ 个微卫星位点ＴＰ５３（１７ｐ１３－１）、ＴＨＲＡ１（１７ｑ１１－２１２）、Ｄ１７Ｓ５７９（１７ｑ１２２１）、Ｄ１７Ｓ８５５（１７ｑ２１） 的ＭＩ和ＬＯＨ。结果　３５ 例ＮＳＣＬＣ中,１７ 号染色体ＭＩ和（或）ＬＯＨ的发生率为６３％ （２４／３５）,其中ＭＩ为４０％ （１４／３５） ,ＬＯＨ 为３１％ （１１／３５）。同时表现有ＭＩ和ＬＯＨ 为９％ （３／３５） 。早期ＮＳＣＬＣ（ Ⅰ期和Ⅱ期） １７ 号染色体ＭＩ和（ 或）ＬＯＨ 发生率为７９％ （１５／１９）,明显大于晚期（ Ⅲ期）ＮＳＣＬＣ（４４％ ,７／１６,Ｐ＜０－０５） 。无纵隔淋巴结转移的ＮＳＣＬＣ的ＭＩ和（ 或）ＬＯＨ 发生率（８７％ ） 亦明显大于已有纵隔淋巴结转移者（４８％ ）,Ｐ＜ ０－０５。ＭＩ和（ 或）ＬＯＨ 在不同肿瘤组织类型以及不同组织细胞分化程度之间差异无显著性,Ｐ＞０．０５。结论　１７ 号染色体ＭＩ和ＬＯＨ 在ＮＳＣＬＣ的发生中可     

胃癌组织5q微卫星不稳定性与APC/MCC基因杂合性缺失的研究

目的探讨５ｑ微卫星不稳定性（ＭＳＩ）与ＡＰＣ／ＭＣＣ基因杂合缺失（ＬＯＨ）的关系。方法应用ＰＣＲ－ＳＳＬＰ及ＰＣＲ－ＲＦＬＰ技术分析５２例手术切除胃癌组织中ＭＳＩ及ＡＰＣ／ＭＭＣ基因ＬＯＨ。结果５ｑＭＳＩ检出率为３４．０％（１６／４７）,ＡＰＣ／ＭＣＣ基因ＬＯＨ率为３１．４％（１１／３５）。早期胃癌５ｑＭＳＩ阳性率为６６．７％（２／３）,ＡＰＣ／ＭＣＣＬＯＨ率为５０％（１／２）;进展期分别为３１．８（１４／４４）,３０．３％（１０／３３）。两组间无显著差别（Ｐ＞０．０５）。ＭＳＩ及杂合缺失与肿瘤大小、浸润深度、淋巴结转移及临床分期无关。粘液（印戒）细胞癌ＡＰＣ／ＭＣＣＬＯＨ率（５５．６％）显著高于高、中分化管状腺癌（Ｐ＜０．０５）。胃、肠两型胃癌５ｑＭＳＩ及ＡＰＣ／ＭＣＣＬＯＨ差异无显著性及５ｑＭＳＩ与ＡＰＣ／ＭＣＣＬＯＨ无相关性（Ｐ＞０．０５）。结论染色体５ｑＭＳＩ有ＡＰＣ／ＭＣＣ基因ＬＯＨ在两型胃癌的早期发生及发展中起一定作用。染色体５ｑ可能是胃癌的易感部位。     

胃癌微卫星不稳定性研究

为了研究微卫星不稳定性（ＭＳＩ）在胃癌发生中的作用，使用ＰＣＲ为基础的方法检测５０例胃癌活检标本的ＭＳＩ。结果发现：胃癌ＭＳＩ阳性率为３４％（１７／５０），其中两个位点ＭＳＩ均阳性者占ＭＳＩ阳性病例的５８．８％（１０／１７），３例早期胃癌ＭＳＩ均阳性，进展期胃癌ＭＳＩ阳性率为２９．８％（１４／４７）。中—高分化腺癌ＭＳＩ阳性率（６０％）显著高于低分化腺癌（１９．４％）（Ｐ＜０．０５）。ＭＳＩ与胃癌部位、大小、Ｌａｕｒｅｎｓ分型、淋巴结转移、浆膜浸润及分期无明显相关。以上结果提示，ＭＳＩ在胃癌的发生中可能起重要作用，是胃癌的一种早期分子标志。检测ＭＳＩ可能成为胃癌高危人群的筛选、胃癌早期诊断的有用指标     

β-受体阻断剂和血管紧张素转换酶抑制剂对心肌梗死患者心率变异影响的比较

为了解β－受体阻断剂和血管紧张素转换酶抑制剂（ＡＣＥＩ）对心肌梗死患者心率变异（ＨＲＶ）的影响，采用惠普系列双通道动态心电图机对５３例急性心肌梗死（ＡＭＩ）和３２例陈旧性心肌梗死（ＯＭＩ）患者进行了ＨＲＶ分析。β－受体阻断剂治疗的ＡＭＩ患者（Ｂ组）与对照组（常规治疗的ＡＭＩ患者即Ｃ组）相比，２４ｈＲＲ间期总体标准差（ＳＤＮＮ）、相邻ＲＲ间期大于５０ｍｓ的百分比（ｐＮＮ５０）均增加（７．２６±３．４４ｍｓｖｓ４．２７±２．０１ｍｓ，１２６．３４±３０．０５ｖｓ９１．４８±２９．２１，Ｐ均＜０．０５），高频带（ＨＦ）增大（８．５３±１．９７ｍｓ２／Ｈｚｖｓ６．７２±２．０８ｍｓ２／Ｈｚ，Ｐ＜０．０５），低频带（ＬＦ）降低（１２．６４±３．０５ｍｓ２／Ｈｚｖｓ１５．３１±４．２１ｍｓ２／Ｈｚ，Ｐ＜０．０１）。ＡＣＥＩ治疗的ＡＭＩ患者（Ａ组）与对照组（ｃ组）相比，ｐＮＮ５０增加（１２３．５９±２７．６３ｖｓ９１．４８±２９．２１，Ｐ＜０．０５），低频与高频的比值降低（２．１３±１．０５ｖｓ２．３５±０．８７，Ｐ＜０．０５），其中伴有心力衰竭者与不伴心力衰竭者相比ＨＲＶ改善较显著。ＡＣＥＩ和β－受体阻断剂对ＯＭＩ患者?     

大肠癌P53蛋白PCNA和CEA的表达与淋巴结转移的关系

目的研究大肠癌Ｐ５３蛋白、增殖细胞核抗原（ＰＣＮＡ）和ＣＥＡ的表达与淋巴结转移的关系．方法应用链霉菌素生物素（ＳＰ）免疫组化法，观察４４例大肠癌Ｐ５３，ＰＣＮＡ的阳性率和ＣＥＡ的表达型式．结果大肠癌Ｐ５３阳性率为５２３％；大肠癌Ｐ５３阳性表达与性别、年龄及肿瘤的部位、分化程度和浸润深度无关（Ｐ＞００５）；大肠癌Ｐ５３阳性者其淋巴结转移率较阴性者高（１４／２３，６０９％ｖｓ６／２１，２８６％，Ｐ＜００５）；Ｐ５３阳性表达及有淋巴结转移者其细胞增殖活性分别较Ｐ５３阴性表达及无淋巴结转移者高（５５９±１７ｖｓ３７９±１４，Ｐ＜００５；５６２±１５ｖｓ３９６±１７，Ｐ＜００５）；Ｐ５３阳性表达及有淋巴结转移者其ＣＥＡ表型均以胞质型和间质型为主（２１／２３，９１３％ｖｓ１３／２１，６１９％，Ｐ＜００５；１９／２０，９５０％ｖｓ１５／２４，６２５％，Ｐ＜００５）．结论检测Ｐ５３和ＰＣＮＡ表达及ＣＥＡ表型对判断大肠癌的恶性程度，预测其淋巴结转移趋势和预后及指导临床治疗有重要价值．     

连枷样二尖瓣口返流彩色多普勒血流的三维重建(英文)

本研究采用体外血流模型,模拟连枷样二尖瓣（ＦＭＶ）口返流,应用常规彩色多普勒血流显像（ＣＤＦＩ）的返流面积与射流和血流会聚区的三维（３Ｄ）超声重建及实际返流量进行对比研究,评价更复杂的血流（脉冲血流通过ＦＭＶ）状态３Ｄ重建的可行性和准确性。被驱动的血流通过一个模拟ＦＭＶ口,返流口的截面积为０．２４ｃｍ２。仪器使用ＡＴＬ,ＩｎｔｅｒｓｐｅｃＡｐｏｇｅｅ８００彩色多普勒超声仪,探头附着在一种机械臂上,在ＴｏｍＴｅｃ计算机控制下进行０°～１８０°的旋转扫描获得射流和血流会聚区３Ｄ重建的数据。同时磁带记录ＣＤＦＩ图像待后分析。结果显示:ＣＤＦＩＦＭＶ的返流面积与实际返流容积和最大返流量呈中等相关（ｒ＝０．６９,ＳＥＥ＝２．２ｃｍ２,Ｐ＜０．０５和ｒ＝０．６２,ＳＥＥ＝２．５ｃｍ２,Ｐ＜０．０５）。３Ｄ重建后的返流容积与实际返流容积和最大返流量相关良好（ｒ＝０．９６,ＳＥＥ＝７．６ｍｌ,Ｐ＜０．０５和ｒ＝０．９４,ＳＥＥ＝８．４ｍｌ,Ｐ＜０．０１）。血流会聚区３Ｄ重建与实际返流容积相关较好（ｒ＝０．８９,ＳＥＥ＝０．２２ｍｌ,Ｐ＜０．０１）。结论:３Ｄ重建可减低ＣＤＦＩ的某些限制,如增益、贴壁返流和混叠速度等,特别是?     

八肽胆囊收缩素、P物质与无症状心肌缺血和心绞痛发生关系的研究

本文测定了无症状心肌缺血（ＳＭＩ）组（１５例）、心绞痛组（１１例）和对照组（７例）运动试验前后血浆八肽胆囊收缩素（ＣＣＫ－８）、Ｐ物质含量，探讨这两种神经调节肽与ＳＭＩ和心绞痛发生的关系。结果显示：①运动前３组血浆ＣＣＫ－８含量分别为４．５５±２．１８、５．１１±１．５９和５．３９±２．８４ｐｍｏｌ／Ｌ，３组之间比较无明显差异；运动后３组血浆ＣＣＫ－８含量分别为４．９１±１．０８、８．５６±１．５７和５．７３±２．４６ｐｍｏｌ／Ｌ，心绞痛组明显高于ＳＭＩ和对照组（Ｐ＜０．０１）。②运动前３组血浆Ｐ物质含量分别为２．１３±０．２８、２．１０±０．２１和２．１３±０．１６ｎｍｏｌ／Ｌ，３组间比较无明显差异；运动后３组分别为２．２５±０．２１、２．４６±０．２０和２．１８±０．１２ｎｍｏｌ／Ｌ，心绞痛组明显高于ＳＭＩ组和对照组（Ｐ＜０．０２）。结果表明：高血浆ＣＣＫ－８、Ｐ物质含量可能参与心绞痛的发生，心肌缺血时无症状可能与血浆ＣＣＫ－８、Ｐ物质含量未升高有关。     

大鼠压力反射敏感性可预测缺血性心律失常严重程度

以冠脉结扎方法制备大鼠急性心肌梗塞（ＡＭＩ）模型，观察压力反射敏感性（ＢＲＳ）与ＡＭＩ心律失常的关系，发现ＡＭＩ时发生室颤（ＶＦ）的动物ＢＲＳ明显低于未发生室颤者，ＢＲＳ值分别为２．０±１．１ｍｓ／ｋＰａ对４．８±１．６ｍｓ／ｋＰａ（Ｐ＜０．０１）．以心律失常积分进行心律失常严重程度评定，发现ＢＲＳ与ＡＭＩ时的心律失常积分呈负相关，ｒ＝－０．６２７，Ｐ＜０．０１。这一结果提示ＢＲＳ低的动物易发生ＡＭＩＶＦ；ＢＲＳ可作为ＡＭＩ心律失常严重程度预测的指标。     

大肠癌患者促胃液素检测的临床意义

目的研究大肠癌患者血清及癌细胞内促胃液素（Ｇａｓ）水平及临床意义．方法采用ＲＩＡ法检测３５例大肠癌患者血清和癌细胞及癌旁粘膜细胞内Ｇａｓ水平．结果大肠癌患者术前、术后血清Ｇａｓ水平与对照组无显著差异（Ｐ＞００５），根治术后明显低于术前（２９ｎｇ／Ｌ±５ｎｇ／Ｌｖｓ３５ｎｇ／Ｌ±１２ｎｇ／Ｌ，ｔ＝２７７２，Ｐ＜００１），在高分化（３６ｎｇ／Ｌ±１６ｎｇ／Ｌｖｓ２８ｎｇ／Ｌ±５ｎｇ／Ｌ）和中分化腺癌组中（３８ｎｇ／Ｌ±７ｎｇ／Ｌｖｓ２７ｎｇ／Ｌ±３ｎｇ／Ｌ）差异显著（ｔ＝２１５２和２３５６，Ｐ＜００５）．大肠癌细胞内Ｇａｓ水平明显高于癌旁３ｃｍ和６ｃｍ粘膜（２１３ａｇ／细胞±７２ａｇ／细胞ｖｓ１４７ａｇ／细胞±３６ａｇ／细胞，１３９ａｇ／细胞±３２ａｇ／细胞；ｔ＝４８９１和５６１３，Ｐ＜００１）和正常粘膜（１３６ａｇ／细胞±４６ａｇ／细胞；ｔ＝２５３４，Ｐ＜００５），高分化腺癌明显高于低分化和粘液腺癌（２４１ａｇ／细胞±７８ａｇ／细胞ｖｓ１６１ａｇ／细胞±４６ａｇ／细胞，ｔ＝２５０５，Ｐ＜００５）．结论大肠癌细胞可通过自分泌方式分泌Ｇａｓ，Ｇａｓ升高是大肠癌分化良好的标志     

Clinical features, diagnosis, treatment and prognosis of multiple primary colorectal carcinoma

AIM: To investigate the clinical features, diagnosis, treatment and prognosis of multiple primary colorectal carcinomas (MPCC). METHODS: A retrospective analysis of 37 patients with MPCC from 1974 to 1998 was carried out. RESULTS: The incidence of MPCC was 2.74%(37/1 348) in patients with primary colorectal carcinomas, 15 cases of them were patients with synchronous carcinomas (SC) and 22 cases were diagnosed as metachronous carcinomas (MC). Most tumors were located in the right colon and rectum. Fifty-five percent (12/22) of MC were diagnosed within 3 years after tumor resection and 41%(9/22) of MC occurred after 8 years. Radical resections were performed in all patients except for 1 case. The 5-year survival rate of SC was 72.7%(8/11) and that of MC after the first cancer and second cancer was 71.4%(15/21) and 38.9%(7/18), respectively. CONCLUSION: The results indicate the importance of complete preoperative examination, careful intraoperative exploration and periodic postoperative surveillance. Early diagnosis and radical resection can increase survival rate of MPCC.     

Microsatellite Instability of Gastric and Colorectal Cancers as a Predictor of Synchronous Gastric or Colorectal Neoplasms

Background/Aims

Microsatellite instability (MSI) plays a crucial role in gastrointestinal carcinogenesis. The aim of this study was to clarify whether MSI is a useful marker for predicting synchronous gastric and colorectal neoplasms.

Methods

Consecutive patients who underwent both esophagogastroduodenoscopy and colonoscopy before the resection of gastric or colorectal cancers were included. MSI was analyzed using two mononucleotide and three dinucleotide markers.

Results

In total, 434 gastric cancers (372 microsatellite stability [MSS], 21 low incidence of MSI [MSI-L], and 41 high incidence of MSI [MSI-H]) and 162 colorectal cancers (138 MSS, 9 MSI-L, and 15 MSI-H) were included. Patients with MSI gastric cancer had a higher prevalence of synchronous colorectal cancer, colorectal adenoma, and gastric adenoma than those with MSS gastric cancers (4.8% vs 0.5%, p=0.023; 11.3% vs 3.2%, p=0.011; 3.2% vs 1.2%, p=0.00, respectively). The prevalence of synchronous colorectal adenomas was highest in MSI-L gastric cancers (19.0%), compared with MSI-H (7.3%) or MSS (3.2%) gastric cancers (p=0.002). In addition, there were no significant differences in the prevalence rates of synchronous colorectal adenoma among the MSI-H (13.3%), MSI-L (11.1%), and MSS (12.3%) colorectal cancers (p=0.987).

Conclusions

The presence of MSI in gastric cancer may be a predictor of synchronous gastric and colorectal neoplasms, whereas MSI in colorectal cancer is not a predictor of synchronous colorectal adenoma.     

Microsatellite instable double primary cancers of the colorectum and stomach exhibit less favorable outcome

AIM: To ascertain the adequacy of the microsatellite instability (MSI) as a prognostic indicator by assessing MSI status of patients with double primary gastric and colorectal cancer (DPGCC). METHODS: Sixteen patients were studied, all of whom exhibited sporadic DPGCC, and had no family history of hereditary non-polyposis colorectal cancer, according to the Amsterdam criteria. A total of 32 cancers from 16 DPGCC patients, and 216 single primary CRC, were assessed for MSI in 5 microsatellite loci, BAT25, BAT26, D2S123, D5S346, and D17S250. RESULTS: MSI was observed in 6 (37.5%) of 16 GC and 4 (25.0%) of 16 CRC. Thirty tumors (13.9%) out of 216 single primary CRC and one tumor (16.7%) out of 6 double primary CRC were found to be microsatellite unstable. Of the 6 GC with MSI in DPGCC, 5 (31.3%) were MSI-high and one (6.3%) was MSI-low. In 5 of 16 DPGCC patients, the cancer recurred in or adjacent to the anastomosis or metastasized to the kidney or lung. The MSI-high DPGCC cases were associated with a younger age of onset (47.5 years vs62.5 years), higher frequency of lymph node metastasis (100% vs 25%), and advanced Dukes stage (C, 100% vs 41.7%), as well as a higher frequency of recurrence or metastasis (100% vs 8.3%). Only recurrence or metastasis showed statistical significance by Fisher's exact test. CONCLUSION: Our data suggest that MSI may play an important role in the development of DPGCC, and that it may be used clinically as a molecular predictive marker for recurrence or late metastasis of DPGCC.     

CpG island methylation as an early event during adenoma progression in carcinogenesis of sporadic colorectal cancer

BACKGROUND AND AIMS: CpG island methylation is present in various tumors, including colorectal carcinomas, and is thought to be an important mechanism in carcinogenesis. We evaluated the methylation status of primary colorectal tumors to determine its role in the adenoma to carcinoma sequence. METHODS: The methylation status of APC, THBS1, MGMT, hMLH1 and GSTP1, as determined by methylation specific PCR (MSP), and microsatellite instability (MSI) using three mononucleotide markers were assessed in 40 colorectal adenomas and 36 adenocarcinomas. The correlations of methylation status and MSI with the clinicopathologic parameters of the tumors were determined. RESULTS: Of the 40 adenomas, 24 (60%) were methylated at one or more loci, and 12 (30%) at two or more loci (CpG island methylation phenotype-high, CIMP-H). Of 36 carcinomas, 27 (75%) were methylated at one or more loci and 11 (30.5%) at two or more loci (CIMP-H). THBSI was the most frequently methylated locus in both adenomas (n = 19, 47.5%) and carcinomas (n = 16, 44.4%). Overall, methylation status of adenomas and carcinomas did not differ significantly (P = 0.53), nor did the methylation status of individual genes. For adenomas, size (P = 0.049) and histologic classification of the villous components (P = 0.018) were each associated with methylation status. For carcinomas, however, no clinicopathologic variable was related to methylation status. MSI was detected in three adenomas (7.5%) and five carcinomas (13.9%), and was closely correlated with hMLH1 methylation (P < 0.001). CONCLUSIONS: In colorectal tumors, CpG island methylation of tumor suppressor genes appears to be common and may be involved in the progression of adenomas.     

Screening for defective DNA mismatch repair in stage II and III colorectal cancer patients.

BACKGROUND & AIMS: Colorectal cancers associated with the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome usually present in younger patients, show loss of mismatch repair (MMR) gene expression, and exhibit microsatellite instability (MSI). About 12% of sporadic colorectal cancers also show MMR loss and MSI. The aims of this study were to evaluate MMR loss and MSI in relation to patient age, sex, tumor stage, and site in the large bowel. METHODS: Tissue microarrays were created from 1020 stage II and III colorectal cancer cases and immunohistochemical staining performed to detect expression of the 2 major MMR proteins, hMLH1 and hMSH2. MSI was determined using the BAT-26 mononucleotide repeat. RESULTS: Ten percent of tumors showed loss of hMLH1 expression and 1.2% showed loss of hMSH2 expression. hMLH1 loss was more frequent in women (P < .001), older patients (P = .004), earlier stage tumors (P = .0001), and proximal colon tumors ( P < .0001). In contrast, tumors showing hMSH2 loss were more frequent in younger (P < .001), male (P = .05) patients and were distributed evenly between the proximal colon and distal colon/rectum. Eleven percent of tumors were MSI+ and these showed similar age, sex, stage, and site characteristics as tumors with hMLH1 loss. Discordance between MMR loss and MSI+ was found in 24 of 983 (2.4%) tumors. Of the 231 patients aged <60 years at diagnosis, 12 (5.2%) showed loss of hMLH1 and 8 (3.5%) showed loss of hMSH2. CONCLUSIONS: Routine immunohistochemical screening for MMR loss in younger colorectal cancer patients may provide a useful, first-step screening tool for the population-based detection of HNPCC.     

The role of clinical criteria, genetic and epigenetic alterations in Lynch-syndrome diagnosis

Lynch syndrome (hereditary nonpolyposis colorectal cancer, HNPCC) represents 1-3% of all diagnosed colorectal cancers (CRCs). This study aimed to evaluate the benefit of clinical criteria and several molecular assays for diagnosis of this syndrome. We examined tumors of 104 unrelated clinically characterized colorectal cancer patients for causal mismatch repair (MMR) deficiency by several methods: microsatellite instability (MSI) and loss of heterozygosity (LOH) presence, MMR protein absence, hypermethylation of MLH1 promoter and germline mutation presence. Twenty-five (24%) patients developed CRCs with a high level of MSI (MSI-H). Almost all (96%) had at least one affected relative, while this simple criterion was satisfied in only 22% (17/79) of individuals with low level MSI or stable cancers (MSI-L, MSS). Using strict Amsterdam criteria, the relative proportion of complying individuals in both sets of patients (MSI-H vs. MSI-L and MSS) decreased to 68% and 9%, respectively. The right-sided tumors were located in 54% of MSI-H persons when compared to 14% of cancers found in MSI-L or MSS patients. In 16 MSI positive patients with identified germline mutation by DNA sequencing, the gene localization of mutation could be indicated beforehand by LOH and/or immunohistochemistry (IHC) in four (25%) and 14 cases (88%), respectively. The IHC findings in MSI-H cancers with methylation in distal or both regions of MLH1 promoter have not confirmed the epigenetic silencing of the MLH1 gene. None of the patients with MSIL or MSS tumors was a carrier of the MLH1 del616 mutation, despite seven of them meeting Amsterdam criteria. The effective screening algorithm of Lynch-syndrome-suspected patients consists of evaluation of Bethesda or Revised Bethesda Guidelines fulfilling simultaneous MSI, LOH and IHC analyses before DNA sequencing. Variable methylation background in MLH1 promoter does not affect gene silencing and its role in Lynch-syndrome tumorigenesis is insignificant.     

胃癌微卫星不稳定性和抑癌基因杂合缺失

目的研究微卫星不稳和抑癌基因缺失在胃癌发生中的作用．方法采用ＰＣＲ为基础的方法,检测了５３例胃癌中６个微卫星标记突变及ＡＰＣ／ＭＣＣ和ＤＣＣ基因杂合缺失（ＬＯＨ）．结果胃癌微卫星不稳的检出率为３２１％（１７／５３）．７例（１３２％）为微卫星高频率不稳（３个以上微卫星标志）,１０例（１８９％）为微卫星低频率不稳（１或２个微卫星标记）．肠型胃癌微卫星高频率不稳的发生率（２５０％）显著高于弥漫型胃癌（３４％）（Ｐ＜００５）．高频率不稳组未发现有ＡＰＣ,ＭＣＣ和ＤＣＣ基因ＬＯＨ,微卫星高频率不稳与ＡＰＣ／ＭＣＣ和ＤＣＣ基因ＬＯＨ呈负相关．结论微卫星不稳在部分胃癌,特别是肠型胃癌早期发生中起重要作用,高频率不稳胃癌与遗传性非息肉大肠癌有共同的特点．与此相反,低频率不稳和无不稳胃癌可能通过ＬＯＨ病理途径发生     

Clinical usefulness of microsatellite instability test in Korean young patients with high-risk features associated with adenoma

The aim of this study was to determine the correlation between microsatellite instability (MSI) and young age in patients with advanced colorectal adenomas. We retrospectively analyzed young patients (≤40years of age) with advanced adenomas (n=84) between January 1996 and December 2006. We randomly selected the control group as patients≥50years of age with advanced adenomas (n=84) during the same time period. Of these patients, the MSI test and MLH1 immunohistochemistry were performed in the available tissue samples from patients with advanced adenomas. The number of patients who had the two tests was 52 in the young group and 49 in the old group. The monomorphic nature of the BAT26 panel for MSI analysis was used without comparison of normal tissue. MSI was detected in three young patients (n=52) and none of the old patients (n=49). There was no statistical difference between the two groups (P=0.243). All three young patients with MSI had a strong family history of colorectal cancer. MSI analysis was not a useful method of screening for HNPCC in young patients with advanced colorectal adenoma, at least in cases without a family history of colorectal cancer.     

Distinct relationship between polypoid growth type and sporadic colorectal carcinomas with microsatellite instability.

BACKGROUND/AIMS: This study was carried out to clarify whether colorectal carcinomas with MSI (microsatellite instability) is correlated with growth types of invasive carcinomas. METHODOLOGY: Samples of tumor tissue and adjacent normal mucosa were obtained from 45 patients with sporadic advanced colorectal cancer. The MSI was assessed by the mobility shift assay of microsatellite and VNTR (variable numbers of tandem repeat) alleles using 12 markers. Tumors with four or more positive loci were determined to be MSI positive. The polyadenine tract (A)10 of the third exon in TGF beta RII was also assessed by mobility shift assay of DNA fragments amplified with primers. Histological examination was performed to divide all tumors into polypoid growth carcinoma and nonpolypoid growth carcinoma, according to Shimoda et al.'s classification. RESULTS: Ten of 11 cases with MSI had a 1-base pair deletion in a polyadenine tract in the TGF beta RII gene. Fifteen cases showed polypoid growth and 30 cases indicated nonpolypoid growth. There were 9 polypoid growth cases and 2 nonpolypoid growth cases with MSI, while there were 6 polypoid growth cases and 28 nonpolypoid growth cases without MSI. Colorectal cancer cases with MSI had a significantly higher incidence of cases with polypoid growth (9/11) compared to those without MSI (6/34) (P = 0.0004). CONCLUSIONS: Sporadic colorectal carcinomas with MSI tend to show a polypoid growth type. We think that there are two types including "adenoma-carcinoma sequence" type and "RER" type in colorectal carcinomas that show adenoma-carcinoma progression.     

Mutation analysis of APC gene in gastric cancer with microsatellite instability

AIM：To evaluate the role of APCmutation in gastric carcinogenesis and to correlate APC mutation with microsatellite instability(MSI)in gastiric carcinomas.METHODS:APC mutation was measured with multiplexPCR,denaturing gradient gel electrophoresis and DNAsequencing;and MSIwas analyzed by PCR-based methods.RESULTS:Sixty-eight cases of sporadis gastric carcinoma were studied for APCmutation at exon15and MSI,APC mutaions were detected in15(22.1%)gastric cancers,Frequence of APCmutation(33.3%)in in testinal type of gastric ancer was significantly higher than that in diffuse type(13.1%,P&lt;0.05).On the contrary.on association was observed dbtween APC mutation and tumor size,differentiation,depth of invasion,metastasis or clinical stages.Using five microsatellite markers.MSIin at least one locus was detected in 17of68(25%)of the tumors analyzed,APC mutations were all detected in MSI-L(only one locus,n=9)orMSS(tumor lacking MSI or stable,n=51),but no mutation was found in MSI-H(≥2loci,n=8).CONCLUSION:APC mutation is involved in carcinogenesis of intestial type of gastric cancer and is independent of MSI phenotype but related to the LOH pathway in gastri cancer.