【作者】 邵耘；

【导师】 张小勇； 赵志泉；

【作者基本信息】 南京医科大学 ， 消化， 2003， 硕士

【摘要】 目的：本研究通过在胃癌和癌前病变中的异型增生、肠化组织中检测微卫星不稳定性(microsatellite instability，MSI)的发生情况及其特点，观察MSI在胃癌发生、发展过程中的变化情况，探索这一早期分子异常事件在胃癌发生中的重要作用，为寻找胃癌早期诊断的分子标志物提供重要线索。 方法：收集100例石蜡标本，其中胃癌30例、不伴癌的异型增生和肠化分别为30例、40例，提取病变组织和相应正常组织的DNA，采用1997年美国国立癌症研究院(NCI)推荐的5个微卫星位点(Bat-25、Bat-26、D5S346、D17S250和D5S123)，应用银染PCR-SSCP技术来检测5个位点的不稳定性。根据实验结果将肿瘤分为三类：第一类：高频微卫星不稳定(high frequency MSI，MSI-H)，即突变的微卫星位点数目≥30％～40％；第二类：低频微卫星不稳定(low frequency MSI，MSI-L)：突变的微卫星位点数目低于30％；第三类：微卫星稳定(microsatellite stable，MSS)：无突变的微卫星位点。 结果：胃癌组织MSI的发生率为23.3％，其中3例表现MSI-H；4例表现MSI-L；其余23例为MSS。MSI现象在BAT-26位点的发生率最高，为13.3％，但各位点之间并无统计学差异性。MSI胃癌与MSS胃癌在性别、年龄、细胞分化程度、淋巴结转移及TNM分期方面无统计学差异，但胃窦癌MSI的发生率显著高于贲门癌(P=0.044)。异型 南京医科大学硕士学位论文增生组织的MSI发生率为30o，其中7例为MSI－L，2例为MSI－H。2级以上异型增生组织的 MSI阳性率高于 l级异型增生门．3OVS 25O），但统计学分析无显著性意义。MSI与MSS的异型增生在性别、年龄方面的差异亦无显著性。肠化组织 MSI发生率 20o，除 1例 MSI－H外，其余7例均表现MSI工。男性的MSI发生率5o门a0），女性的MSI发生率35o门o 0，性别差异性显著（P＝0．044）。17例轻度肠化均表现为MSS，中度肠化生的MSI阳性率达3牛8％，两组之间MS互发生率差异性显著（P刃．013）。 结论：MSI可能是胃癌发生、发展过程中的一种独特的分子机制，与某种临床病理特征相关；MSI在慢性胃炎驹上的胃癌癌前病变组织中的存在，提示MSI可能是胃癌的多步骤发生过程中的早期而重要的分子事件；对表现为MSI的胃癌癌前病变患者加强随访观察，将可能有助于早期胃癌诊断率的提高。更多还原

【Abstract】 Background: Gastric cancer(GC) is one of the most common malignant neoplasms among the world. Genetic alterations have been show to play roles in gastric carcinogenesis including abnormalities in proto-oncogenes, tumor suppressor genes, cell cycle regulator genes, tissue invasion-related genes, and mismatch repair genes. lintestinal metaplasia (IM) and dysplasia are considered precursor lesion of GC, but the genetic mechanism of early gastric carcinogenesis are not well knownObjective: To observe the changeable patterns of microsatellite instability (MSI) in GC and precancerous lesions, including IM and dysplasia. And to defermine the potential significance of MSI in the multistep gastric carcinogenesis pathway.Methods: We investigated MSI status in 30 flat dysplasias and 40 IMs without GC, and 30 GCs. Silver staining single strand conformation polymorphis polymerize chain reaction (PCR-SSCP) was used to screen 5 MSI markers , recommended by the National Cancer Institute, in formalin-fixed, paraffin-embeded tissues and corresponding normal gastric tissues. In this study, a high incidence of MSI (MSI-H) was defined as samplescontaining 30% or more MSI positive loci, a low incidence of MSI (MSI-L) as samples which had less than 30% loci instability, and MSS when samples displaying no alterations in 5 loci.Results: The abnormal shifting of the single-strand DNA was identified in 7 ( 23.3% ) out of GC, in 9 ( 30% ) out of dysplasia and in 8 ( 20% ) out of IM samples. Three ( 10% ) tumors, two ( 6.7% ) dysplasia and one ( 2.5% ) IM displayed MSI-H. MSI-L was detected in 13.3% of the tumors, in 23.3% dysplasia and in 17.5% IM samples. GC with MSI was associated with distal location of the tumors ( P=0.044 ), but no association was defined between MSI and age, gender, differentiation, lymph node metastasis and PTNM stage. Although MSI showed a trend for high-grade dysplasia, the differences were not significant. MSI was more likely observed in female with IM ( P=0.044 ) and in moderate-grade IM tissues ( 34.8% versus 0; P=0.013 ).Conclusions: The frequency of MSI in detected GC and precancerous lesions are almost the same when compared with previously reported data. MSI occurs not only in gastric adenomas and flat dysplasia coexisting with GC, but also in dysplasia without carcinoma. The progressive accumulation of MSI in areas of dysplasia and IM may contribute to GC development, suggesting that genetic instability may be an early somatic event of multistep gastric carcinogenesis.更多还原