胃癌中PTEN异常表达与围基因微卫星的杂合性缺失

目的　观察胃癌中PTEN基因异常表达与围基因微卫星的杂合性缺失 (LOH) ,探讨其在胃癌演进中的作用。方法　利用PCR SSCP检测进展期胃癌中PTEN围基因微卫星位点 (D10S5 4 1、D10S5 83、D10S16 87)的LOH ;采用RT PCR和免疫组化检测正常胃黏膜和胃癌中PTEN基因mRNA和蛋白表达 ;比较PTEN表达与淋巴结转移的关系 ;分析PTENmRNA表达与微卫星位点LOH及PTEN蛋白表达的关系。结果　进展期胃癌中D10S5 4 1、D10S5 83及D10S16 87微卫星位点LOH总的发生频率为2 8.6 % ;正常胃黏膜、早期胃癌和进展期胃癌的PTENmRNA阳性率分别为 80 .4 %、4 5 .5 %和 32 .1% ,其蛋白阳性率分别为 78.6 %、36 .4 %和 2 8.6 % ;早期和进展期胃癌中 ,PTENmRNA和蛋白阳性率低于正常胃黏膜 (P <0 .0 5 ) ;进展期胃癌中 ,PTENmRNA表达与其围基因微卫星LOH呈正相关 (Pearson相关系数 =0 .2 6 6 ) ;PTENmRNA与蛋白表达具有显著的一致性 (P <0 .0 5 ) ;PTENmRNA和蛋白表达与进展期胃癌淋巴结转移有关 (P <0 .0 5 )。结论　PTEN基因在胃癌发展不同阶段表达下调 ,并与其围基因微卫星LOH密切相关 ,微卫星LOH可能是其低表达的分子基础之一 ,PTEN基因表达异常与围基因微卫星LOH在胃癌发生和演进中具有重要意义。

Altered expression of PTEN gene and LOH of its epigenetic microsatellite in gastric carcinoma

Objective To investigate the expression of PTEN and loss of heterozygos ity (LOH) of its epigenetic microsatellite in gastric carcinoma and explore thei r roles in progression of gastric carcinoma. Methods LOH of epigenetic microsat ellites of PTEN (D10S541,D10S583 and D10S1687) in advanced gastric cancer was d etected by PCR-SSCP. Expression of PTEN mRNA and protein in normal gastric muco s a and gastric cancer was evaluated by RT-PCR and SABC immunohistochemistry,res p ectively. The relationship between expression of PTEN mRNA and protein and lymph node metastasis or LOH of microsatellites was discussed. Results LOH of D10S5 41,D10S583 and D10S1687 was found in 37.5%(21/56) of advanced gastric cancers. The positive rates of PTEN mRNA expression were 80.4%(45/56),45.5%(5/11) and 3 2.1%(18/56) in normal mucosa,early and advanced gastric carcinomas,respectivel y,while 78.6% (44/56),44.5% (5/11) and 28.6% (16/56) at the protein level. PT EN mRNA and protein were less frequently expressed in early and advanced gastric carcinomas than that in normal gastric mucosa ( P <0.05). There was positive corr elation between PTEN mRNA expression and LOH of microsatellites in advanced gast ric carcinomas. PTEN protein expression paralleled with its mRNA expression( P < 0.05). The expression of PTEN mRNA and protein was negatively correlated with ly mph node metastasis of advanced gastric carcinomas ( P <0.05). Conclusion Down-r egulated expression of PTEN gene is found in different stages of gastric carcino ma,and is closely correlated with LOH of its epigenetic microsatellites,which probably is its underlying molecular mechanisms. It suggests that altered PTEN g ene contributes to tumorigenesis and progression of gastric carcinomas.