胸腺鳞癌微卫星不稳定和杂合性缺失的初步探讨

目的 检测胸腺鳞癌微卫星不稳定(MSI)和杂合性缺失(LOH)发生频率,以探讨胸腺鳞癌MSI现象的合适微卫星(MS)位点.方法 选择5个微卫星多态性标记,从石蜡包埋的存档标本中选取9例肿瘤组织和其对应的自身正常组织,提取DNA后用PCR扩增,6%聚丙稀酰胺凝胶电泳,银染显色后进行MSI和LOH分析.结果 9例胸腺鳞癌均出现MSI或LOH.在所检5个位点中D6S1708、TP53、DM、D11S988和D8S136微卫星不平衡发生率分别为66.7%(6/9)、33.3%(3/9)、33.3%(3/9)、33.3%(3/9)和0%(0/9).D6S1708遗传学改变多为LOH(5/6),D11S988位点仅见于LOH.结论 D6S1708、TP53、DM和D11S988可以作为研究胸腺鳞癌微卫星的位点;微卫星不平衡可能在胸腺鳞癌的发生中起一定作用,其与胸腺鳞癌临床病理特点的关系尚需进一步探讨.     

前列腺癌中微卫星不稳定及其临床意义

目的:探讨微卫星不稳定(MSI)与前列腺癌临床病理特征关系。方法:选取82例前列腺癌患者的手术切除标本和相应的癌旁组织,采用PCR扩增和变性凝胶电泳-银染法检测MSI,分析其与临床病理特征的关系。结果:82例前列腺癌中,微卫星稳定(MSS)、低微卫星不稳定(MSI-L)及高微卫星不稳定(MSI-H)发生率分别为64.6%(53/82)、25.6%(21/82)、9.8%(8/82)。前列腺癌组织中MSI发生与患者血清PSA和Gleason评分存在相关性(P0.05),与年龄、TNM分期、有无淋巴结转移等临床病理因素无明显相关性(P0.05)。结论:MSI前列腺癌侵袭性较低,可能是预后良好的标志。     

微卫星不稳定状态对散发性直肠癌预后的影响

目的 研究汉族人散发性直肠癌的微卫星不稳定状态(microsatellite instability,MSI)及其与临床病理学和预后的关系.方法 应用PCR扩增患者肿瘤组织和对应正常组织的DNA,分析微卫星不稳定状态,并采用单因素、多因素分析评估预后.结果 MSI分为高频率微卫星不稳定(microsatellite instability.high,MSI-H)、低频率微卫星不稳定(microsatellite instability-low,MSI-L)、微卫星稳定(microsatellite stability,MSS).93例直肠癌患者中,MSI-H 11例(12%),MSI-L和MSS分别为23例(25%)和59例(63%).与MSI-L和MSS相比,大多数MSI-H为高分化肿瘤、患者年龄小、术前CEA水平高、总的生存率高.结论 在汉族人群散发性直肠癌中,MSI-H发生率高,且MSI是一个相对较好的预后预测指标.     

胃癌微卫星不稳定性及其与临床病理生物学的关系

目的探讨微卫星不稳定性 (MSI)发生与胃癌临床病理生物学行为的关系及其临床意义.方法采用酚氯仿异戊醇法从胃癌组织切片中提取 DNA.组织切片中肿瘤成分不足 50%时采用显微微切割方法.以 PCR为基础的单链构像多态性方法分析胃癌组织分别在 BAT26、 BAT40、 D2S123、 D5S346和 D17S250 5个位点的微卫星不稳定性.结果按照微卫星不稳定性的发生频率将胃癌患者分为 3组 出现 2个或 2个以上微卫星位点不稳定性为高 MSI组( MSI-H);出现 1个位点不稳定性为低 MSI组( MSI-L);无 MSI发生为微卫星稳定组( MSS). 61例胃癌患者中, 12例( 19.7%)为 MSI-H, 11例( 18.0%)为 MSI-L, 38例( 62.3%)表现为 MSS. MSI-L组与 MSS组患者在胃癌各临床病理生物学参数间差异无显著性意义( P >0.05),但这两组与 MSI-H组比较,在肿瘤的发生位置、 Lauré n分型、淋巴结是否转移和肿瘤分期方面差异有显著性意义( P< 0.05). MSI-H型胃癌多发生于胃窦部,多见于淋巴结转移阴性、肠型和较早期胃癌,其发生与患者年龄、性别和肿瘤大小无明显的相关性.结论 MSI-H型胃癌与 MSI-L或 MSS型胃癌具有不同的临床病理学行为, MSI-H型胃癌与肿瘤位置、淋巴结是否转移、 Lauré n分型及肿瘤分期密切相关.微卫星不稳定性可能是胃癌发生的另一分子机制.     

高度微卫星不稳定性对结直肠癌病人的预后作用

微卫星不稳定性 (MSI)在 10 %～ 15%的散发性结直肠癌病人中出现 ,根据 MSI的水平可分为三型 :高度 MSI(MSI- H)、低度 MSI(MSI- L )、微卫星稳定(MSS)。作者通过检测散发性结直肠癌病人 MSI- H,确立 MSI- H与病人预后的关系。方法　 2 38例散发性结直肠癌病人 ,入选条件为 :肿瘤分期符合改良 ACPS- C期 (相当于 TNM 期 ) ,单纯手术治疗 ,未行化疗 ,随访时间至少 5年。从上述病人的石蜡包埋组织中分别提取正常及肿瘤 DNA,通过放射标记的 PCR技术扩增。作者检测了 7个微卫星标志系列 (BAT2 5、BAT2 6、c- myb、D5S346…     

胰腺癌中微卫星不稳定性与错配修复基因表达的相关性研究

本研究检测35例胰腺癌标本中的5个微卫星位点，用单链构象多态性（SSCP）法对标本进行微卫星不稳定（MSI）分析，进一步检测胰腺癌及正常胰腺组织中hMSH2和hMLHl的蛋白表达及启动子CpG岛甲基化状态，分析MSI与胰腺癌错配修复基因表达之间的联系，探讨MSI致癌的可能机制。     

转化生长因子βⅡ受体、胰岛素生长因子Ⅱ受体、凋亡诱导蛋白BAX和转录因子E2F4基因移码突变与胃癌微卫星不稳定性的关系

目的探讨胃癌组织中与细胞增殖、凋亡和转录有关的基因移码突变与微卫星不稳定性（MSI）的关系。方法采用酚．氯仿一异戊醇法从胃癌及切缘正常石蜡组织中提取DNA。组织切片中肿瘤成分不足50％时采用显微切割方法。以聚合酶链反应一单链构象多态性（PCR-SSCP）、直接DNA测序法检测MSI及转化生长因子BII受体（TGFβRⅡ）、胰岛素生长因子Ⅱ受体（IGFⅡR）、凋亡诱导蛋白BAX和转录因子E2F4基因的移码突变。按照MSI的发生频率将胃癌患者分为3组：出现≥2个位点的MSI为高MSI,出现1个位点的MSI为低MSI,无MSI发生为微卫星稳定。结果61例胃癌患者中,12例（19．7％）为高MSI,11例（18．0％）为低MSI,38例（62．3％）为微卫星稳定。TGFβRⅡ、IGFⅡR、BAX和E2F4移码突变检出率分别为12例（19．7％）、3例（4．9％）、4例（6．6％）和10例（16．4％）。12例高MSI胃癌中,有10例TGFβRⅡ基因突变,3例IGFⅡR基因突变,4例BAX基因突变,10例E2F4基因突变;其移码突变率与高MSI发生密切相关。微卫星稳定组的肿瘤中未发现这些基因的突变。结论TGFβRⅡ、IGFⅡR、BAX和E2F4基因编码区重复序列是MSI发生的靶点,这些基因的移码突变在MSI胃癌的发生和发展中起了重要作用。     

胰腺癌微卫星不稳定性、hMLH1启动子甲基化及其蛋白表达研究

目的探讨胰腺癌中微卫星不稳定性（MSI）与hMLH1启动子甲基化及蛋白表达之间的联系，揭示胰腺癌发生的分子机制。方法从35例胰腺癌患者的正常胰腺组织、癌组织中提取DNA；SSCP法检测标本中微卫星不稳定性发生情况；免疫组织化学法检测错配修复基因hMLH1在胰腺癌中的表达情况；MSP法检测hMLH1基因启动子甲基化状态。结果35例胰腺癌中微卫星高度不稳定7例，低度不稳定14例，稳定11例，正常组织中没有出现微卫星不稳定，两者之间差异有统计学意义（P〈0．05）。hMLH1在微卫星不稳定胰腺癌组织中常为缺失表达。在微卫星稳定胰腺癌组织中呈正常表达。35例胰腺癌中hMLH1启动子CpG岛甲基化发生率为60％（21/35）。正常组织中未发现甲基化，两者之间差异有统计学意义（P〈0．05）。结论与胰腺癌有关的错配修复基因hMLH1启动子CpG岛甲基化是hMLH1基因失活的重要机制，而hMLH1的表达失活则可能导致MSI的产生，促进胰腺癌的发生。     

对于Ⅱ期及Ⅲ期微卫星不稳定结肠癌患者BRAF和KRAS突变状态的预后价值

<正>对于早期结直肠癌(CRC)患者来说,微卫星不稳定结肠癌(MSI)比微卫星稳定结肠癌(MSS)具有更好的生存率。BRAF V600E突变与MSS的较差生存率有关,这种突变存在于40%的MSI中且尚未明确此突变是否会导致MSI更差的生存率。KRAS突变对于MSI和MSS的预后价值尚未明确。故de Cuba EM等研究了BRAF对Ⅱ期及Ⅲ期MSI结肠癌患者生存率的     

胃癌微卫星不稳定研究进展

目的探讨胃癌与微卫星不稳定（MSI）的关系。方法查阅国内外相关文献并进行综述。结果 MSI系碱基错配修复系统（MMR）缺陷导致的复制错误;MSI胃癌具有特征性的临床病理学及预后,可通过检测癌前组织以及胃癌组织中的MSI来评估胃癌发生风险和预后;MSI包括核基因MSI（nMSI）和线粒体MSI（mtMSI）。结论MSI在胃癌的发生和发展中起着重要的作用,其可能成为预测癌前病变癌变风险和胃癌临床预后的重要指标。     

Microsatellite instability is not a common feature in medullary breast cancer

Microsatellite instability (MSI) is a form of genomic instability associated with defective DNA mismatch repair in tumors. MSI is found in 85-90% of hereditary nonpolyposis colorectal cancer cases; however, its occurrence in breast carcinogenesis still remains to be clarified. In addition, data are limited on the incidence of MSI in the medullary subtype. The purpose of this study was to investigate the occurrence of MSI in medullary breast cancer (MBC). The study included a total of 16 patients with MBC, nine with typical and seven with atypical histology. The incidence of MSI in five microsatellite loci (D2S123, D3S1611, D17S807, D17S796 and Xq11-12) was determined by comparing paired normal and tumor tissue DNA after PCR amplification from paraffin-embedded tissues. All 16 tumors showed stability at five loci. Although the number of microsatellite markers and DNA samples may limit the value of our results, we conclude that the MSI phenotype is uncommon in human MBC.     

Low frequency of microsatellite instability in hereditary prostate cancer

OBJECTIVE: To investigate whether there is widespread microsatellite instability (MSI) in families with hereditary prostate cancer (HPC). PATIENTS AND METHODS: Eighty-four prostate tumours from 80 Swedish men in 35 families with HPC were screened for genetic instability at microsatellite marker loci BAT-25, BAT-26, BAT-34C4, D2S123 and D17S250. RESULTS: MSI was detected in only five individuals from different families. Three tumours (4%) were unstable at more than two MSI loci and hence classified as high-frequency MSI (MSI-H) according to a previous definition. Interestingly, two of the MSI-H tumours were from patients in families with both HPC and familial colon cancer. CONCLUSIONS: Widespread MSI is a rare event in hereditary prostate cancer, indicating that defective DNA mismatch repair is not an important element in the genesis of HPC.     

多重荧光PCR方法对结直肠癌进行微卫星不稳定检测及其临床价值

目的探讨多重荧光PCR方法检测结直肠癌微卫星不稳定（MSI）及其临床意义。方法将2004-2005年间进行手术治疗的110例结直肠癌患者建立队列，以多重荧光PCR方法检测结直肠癌MSI，并对MSI和微卫星稳定（MSS）结直肠癌患者的临床病理特点进行比较。结果多重荧光PCR方法扩增出所有患者的5个微卫星序列。其中MSI．H10例（8．1％），MSI-L13例（11．8％），MSS为87例（79．1％）。共检测BAT．26变异9例（8．2％）、BAT．25变异11例（10．0％）、D2S123变异11例（10．0％）、D5S346变异6例（5．5％）和D17S250变异8例（7．3％）。MSI-L、MSI．H和MSS组结直肠癌患者年龄比较，差异有统计学意义（P〈0．05）；其他临床病理特点差异无统计学意义（P〉0．05）。结论多重荧光PCR方法检测MSI结果稳定，宜于临床应用；MSI和MSS结直肠癌患者临床病理特点比较未见差异。     

微卫星不稳定对散发性结直肠癌患者预后的影响

目的 探讨微卫星不稳定(MSI)对散发性结直肠癌预后的影响.方法 收集2004年8月至2006年9月南京中医药大学第三附属医院手术治疗并具有完整随访资料的134例结直肠癌病例,根据MSI检测结果 将其分成MSI组和微卫星稳定(MSS)组.采用单因素和多因素预后分析来评估MSI的预后价值.结果 134例患者中MSI组26例,MSS组108例.两组患者术后复发率分别为7.7%(2/26)和35.2%(38/108),差异有统计学意义(P=0.006);两组患者5年生存率分别为92.3%和63.5%,差异亦有统计学意义(P=0.016).经多因素分析,MSI为结直肠癌患者的独立预后因素(P=0.029).结论 微卫星不稳定是影响散发性结直肠癌患者预后的重要因素.

Abstract：

Objective To investigate the role of microsatellite instability (MSI) in Chinese sporadic coloretal cancer. Methods A total of 146 patients with colorectal cancer were treated surgically from August 2004 to September 2006 in the Third Affiliated Hospital of Nanjing University of Traditional Chinese Medicine. Data were collected prospectively. Univariate and multivariable analyses were performed for parameters such as age, gender, tumor location, differentiation, MSI, tumor type, lymph node metastasis,TNM stage, and survival. Results Follow-up was available in 134 patients including telephone call and office visit. MSI(P=0.029), tumor type (P=0.000), TNM stage (P=0.000) were independently associated with survival on Cox regression model. There were 26 patients with MSI, and the 1-, 3-, and 5-year survival rates were 100% , 92.3% , and 92.3% , respectively. The remaining 108 patients had microsatellite stable tumor, and the 1-, 3-, and 5year survival rates were 96.3% , 72.2% , and 63.5% , respectively. The difference was statistically significant(P=0.016). Conclusion Microsatellite instability is an important factor associated with patient survival in Chinese sporadic colorectal cancer.     

膀胱癌染色体微卫星不稳定性及杂合性丢失

目的　探讨染色体微卫星不稳定性（ ＭＳＩ） 及杂合性丢失（ＬＯＨ） 在膀胱癌早期诊断中的意义。　方法　运用位于４ 、５ 、９ 、２１ 号染色体上的四对微卫星标志,结合ＰＣＲ 银染技术,分别检测２２例膀胱癌患者肿瘤组织及尿脱落细胞染色体ＭＳＩ及ＬＯＨ。　结果　肿瘤及尿液标本ＭＳＩ的发生率分别为２３ ％ 、１９ ％ ,ＬＯＨ 发生率分别为４１ ％ 、１８ ％ ,至少有一个位点出现ＭＳＩ或ＬＯＨ 分别为５９ ％ 及３２ ％ 。不同年龄、性别、临床分期、肿瘤组织分级的患者ＭＳＩ与ＬＯＨ 的发生率差异均无显著性（ Ｐ＞０ ．０５） 。　结论　检查尿液中肿瘤脱落细胞的ＭＳＩ及ＬＯＨ 可能成为膀胱癌筛选及监测复发的辅助方法。     

Clinical significance of mutator phenotype and chromosome 17p and 18q allelic loss in gastric cancer

BACKGROUND: Tumour stage is the only reliable prognostic factor for gastric cancer. The molecular anomalies involved in this process have the potential to serve as additional prognostic markers. METHODS: Forty-four gastric cancers, treated by surgery alone, have been analysed for chromosome 17p and 18q allelic loss and for the presence of microsatellite instability (MSI), using microsatellite markers and DNA from paraffin-embedded tumours. RESULTS: Eight cancers showed a MSI-positive (MSI+) phenotype. Among the 36 MSI-negative cancers, chromosome 17p and 18q allelic losses were found in 22 of 34 and 19 of 33 informative cases respectively. Multivariate survival analysis indicated MSI status to be an independent prognostic factor along with the tumour stage. MSI+ cancers were associated with longer patient survival, whereas MSI-negative cancers had a significantly poorer prognosis (P = 0.007), with a median actuarial survival of 24 months. CONCLUSION: MSI status is an independent prognostic factor among gastric cancers at the same stage. Chromosome 17p and 18q status added no additional prognostic information to that of tumour stage. The combined use of tumour stage and MSI status may help in deciding whether patients with advanced gastric cancer require additional therapy other than surgery alone.     

Microsatellite instability in gastrointestinal tract tumours

Although a number of studies have documented microsatellite instability (MSI) in gastrointestinal tumours, the clinical significance is uncertain. In this study the MSI status and clinicopathological features were examined in gastric and colorectal tumours. Eighty-four gastrointestinal tumours were examined for MSI. Normal and tumour DNA isolated from the same patients were analysed at five different microsatellite loci. Clinical features of these patients were also collated and compared with MSI status. High level MSI (MSI-H) (as defined by instability in 2 or more microsatellites) was detected in 6 out of 47 (13%) colon tumours and 6 of 37 (16%) gastric tumours. The frequency of MSI-H between these groups was not statistically significant (P = 0.36). There was no significant correlation with patient age or gender, UICC stage, or degree of differentiation of the tumour. This was true both when analysed as a group, as well as when divided into colon and gastric sites. Our results confirm that a proportion of sporadic tumours from the colon and stomach exhibit an MSI-H phenotype. However, there was no significant relationship between the presence of MSI and any of the clinicopathological characteristics studied.     

微卫星不稳定性检测在遗传性非息肉病性结直肠癌家系遴选中的作用

目的 探讨微卫星不稳定性(MSI)检测在遗传性非息肉病性结直肠癌(HNPCC)家系遴选中敏感性、特异性及临床应用的价值。方法 对12例符合Amsterdam标准的HNPCC患和16例散发性结直肠癌患的肿瘤标本进行微卫星不稳定性检测。结果 若将高微卫星不稳定性(MSI-H)及低微卫星不稳定性(MSI-L)的结直肠癌患作为HNPCC家系的诊断标准,其敏感性为100％,特异性为75％,正确率为81％;若仅将MSI-H的结直肠癌患作为HNPCC家系的诊断标准,其敏感性为100％,特异性为94％,正确率为95％。结论 微卫星不稳定性检测遴选HNPCC家系敏感性和特异性较高,而且两简单、经济,适合在临床广泛应用。     

Microsatellite instability and mismatch repair target gene mutations in cell lines and xenografts of prostate cancer

BACKGROUND: Mismatch repair (MMR) and microsatellite instability (MSI) occur in prostate cancer, but their role has not been well documented. METHODS: In 6 cell lines and 22 xenografts from prostate cancer, PCR and gel electrophoresis were performed to detect MSI by analyzing microsatellite markers BAT-25 and BAT-26 and to detect frameshift mutations in mononucleotide repeats in BAX, IGF2R, MSH3, MSH6, and TGFBR2. RESULTS: Four of 6 (67%) cell lines and 3 of 22 (14%) xenografts showed MSI. At least 1 frameshift mutation was detected in the same 4 (67%) cell lines and in 5 of 22 (23%) xenografts. While MSH3 was frequently mutated in cell lines, BAX and TGFBR2 showed frequent alterations in both cell lines and xenografts. CONCLUSIONS: MSI related to MMR deficiency is relatively frequent in high-grade tumors, and mutations in MSI target genes involved in cell death and proliferation appeared to be selected for during prostatic carcinogenesis.