Liu Ping, Zhang Xiao-Yong, Shao Yun, Zhang Dao-Fu
Department of Oncology, the First Affiliated Hospital of Nanjing Medical University, 300 Guangshou Road, Nanjing 210029, Jiangsu Province, China.
World J Gastroenterol. 2005 Aug 21;11(31):4904-7. doi: 10.3748/wjg.v11.i31.4904.
To investigate the microsatellite instability (MSI) in cancer and pre-cancerous lesions of the stomach and its mechanisms underlying the development of gastric cancer.
Thirty-six gastric cancer samples were obtained from patients undergoing surgery. Forty-one gastric mucosa samples with dysplasia and 51 with intestinal metaplasia (IM) were obtained from patients with chronic gastritis undergoing gastro-endoscopy. Genomic DNA was extracted from the samples. Silver staining single strand conformation polymorphis-polymerize chain reaction (SSCP-PCR) was used to screen MSI markers at 5 loci (Bat-25, Bat-26, D5S346, D17S250, and D2S123) in fresh tissues and formalin-fixed, paraffin-embedded samples and their corresponding normal gastric mucosa.
The abnormal shifting of the single-strand DNA (MSI) was identified in 21 out of 36 (58.3%) gastric cancers. Seven cases showed high-level MSI (two or more loci altered) and 14 showed low-level MSI (one locus altered). Gastric cancer with MSI had a tendency to be located in the distal stomach. MSI was also detected in 11 out of 41 (26.8%) dysplasia samples and in 9 of 51 (17.6%) IM samples respectively. Three cases of dysplasia and one case of IM showed high-level MSI. Eight cases of dysplasia and 8 cases of IM displayed low-level MSI. MIS in IM was found only in moderate or severe-grade IM. No association was detected between MSI and dysplasia grade.
Accumulation of MSI in dysplasia and intestinal metaplasia of gastric mucosa may be an early molecular event during gastric carcinogenesis and may contribute to the acquisition of transformed cell phenotype and the development of gastric cancer.
研究胃癌及癌前病变胃组织中的微卫星不稳定性（MSI）及其在胃癌发生发展中的机制。
从接受手术的患者中获取36例胃癌样本。从接受胃镜检查的慢性胃炎患者中获取41例发育异常的胃黏膜样本和51例肠化生（IM）样本。从样本中提取基因组DNA。采用银染单链构象多态性聚合酶链反应（SSCP-PCR）技术，在新鲜组织、福尔马林固定石蜡包埋样本及其相应的正常胃黏膜中筛选5个位点（Bat-25、Bat-26、D5S346、D17S250和D2S123）的MSI标记。
36例胃癌中有21例（58.3%）检测到单链DNA异常迁移（MSI）。7例为高度MSI（两个或更多位点改变），14例为低度MSI（一个位点改变）。MSI阳性的胃癌倾向于位于胃远端。发育异常样本中41例有11例（26.8%）检测到MSI，肠化生样本中51例有9例（17.6%）检测到MSI。3例发育异常和1例肠化生表现为高度MSI。8例发育异常和8例肠化生表现为低度MSI。肠化生中的MSI仅在中重度肠化生中发现。未检测到MSI与发育异常分级之间的关联。
胃黏膜发育异常和肠化生中MSI的积累可能是胃癌发生过程中的早期分子事件，可能有助于获得转化细胞表型和胃癌的发生发展。
