摘要
目的:探讨胃癌及癌前病变中抑癌基因PTEN和微卫星不稳定(MSI)的变化以及二者的关系.方法:胃癌及癌前病变标本取自中国医科大学附属第一医院内窥镜中心和肿瘤外科手术后,每组30例,PTEN杂合性缺失(LOH)和MS应用PCR-SSCP银染色方法检测,PTEN基因突变通过PCR-SSCPABI测序方法检测,S-P免疫组化检测PTEN蛋白质表达.结果:在萎缩性胃炎无肠化、萎缩性胃炎伴肠化、不典型增生、早期胃癌、进展期胃癌中PTENLOH率和MSI率分别为10%、10%、13.3%、20%、30%和13.3%、16.7%、23.3%、36%、40%.PTEN蛋白质表达在正常胃黏膜为100%,在慢性浅表性胃炎、慢性萎缩性胃炎无肠化、慢性萎缩性胃炎伴肠化、中度不典型增生、重度不典型增生、早期胃癌、进展期胃癌中PTEN蛋白质的表达分别为96.7%、90.0%、76.7%、73.3%、63.3%、60.0%、43.3%.所有病例共检测到3例PTEN突变,这3例均为MSI阳性的进展期胃癌.结论:PTEN缺失及突变与胃癌的浸润转移关系密切,在胃癌的发病过程中,PTEN蛋白呈下调性表达,MSI是胃癌发生的早期分子标志PTEN基因突变常发生在MSI阳性的进展期胃癌中.
AIM: To investigate the changes of tumor suppressor gene PTEN and microsatellite instability (MSI) in gastric cancer and precancerous lesion as well as the relationship between them. METHODS: Samples of gastric cancer and precancerous lesion were collected from endoscopy center and oncology surgery department of China Medical University. There were 30 cases in each group. PCR-SSCP silver staining was used to analyze the loss of heterozygosity (LOH) in PTEN gene and MSI. PTEN mutations were detected by PCR-SSCP and sequencing, and PTEN protein expression was detected by S-P immunohistochemistry. RESULTS: The percentages of PTEN LOH in atrophic gastritis without intestinal metaplasia, atrophic gastritis with intestinal metaplasia, atypical hyperplasia, early-stage gastric cancer, and advanced gastric cancer were 10%, 10%, 13.3%, 20%, and 30%; meanwhile, the proportions of MSI were 13.3%, 16.7%, 23.3%, 36% and 40%, separately. The protein expression of PTEN in normal gastric mucosa was 100%, in chronic superficial gastritis, and it was 96.7%, 90.0%, 76.7%, 73.3%, 63.3%, 60.0% and 43.3% in chronic superficial gastritis, chronic atrophic gastritis without intestinal metaplasia, atrophic gastritis with intestinal metaplasia, moderate atypical hyperplasia, severe atypical hyperplasia, earlystage gastric cancer, and advanced gastric cancer, separately. PTEN mutation was detected in 3 cases, all of whom were found with advanced gastric cancer and positive for MSI.CONCLUSION: Loss and mutation of PTEN gene are closely associated with the invasion and metastasis of gastric cancer. PTEN protein expresion is down-regulated during the pathogenesis of gastric cancer, and MSI is a early molecular marker in the pathogenesis of gastric cancer. PTEN mutation is commonly occurred in MSI-positive gastric cancer.
出处
《世界华人消化杂志》
CAS
北大核心
2008年第22期2470-2475,共6页
World Chinese Journal of Digestology
基金
辽宁省教育厅资助项目
No.20061006~~
关键词
胃癌
癌前病变
PTEN
突变
微卫星不稳定
PTEN
Mutation
Microsatellite instability
Gastric cancer
Precancerous lesion