幼年性息肉病不典型增生分子机制研究

Molecular mechanisms of epithelial dysplasia in juvenile polyposis syndrome

摘要:

目的 幼年性息肉病是一种少见疾病。目前认为其息肉局部可发生不典型增生改变 ,然而其不典型增生的分子机制尚不清楚。该文旨在探讨幼年性息肉病不典型增生的病变机制。方法 应用免疫组化检测 5例幼年性息肉病的 2 4枚不典型增生息肉和 11枚无不典型增生息肉标本以及 5例小儿正常结肠粘膜、32例单发结、直肠幼年性息肉和 10例大肠癌标本的增殖细胞核抗原 (PCNA)、P5 3蛋白 (DO 7)和P2 1waf1蛋白的表达 ;应用原位杂交方法检测上述标本P5 3mRNA的表达。结果 PCNA标记指数均值、P5 3阳性表达率、P5 3阳性面积以及P5 3mRNA阳性表达率在幼年性息肉病不典型增生组均明显高于无不典型增生组 ;P2 1waf1阳性表达在上述两组间比较差异无显著性 ;P5 3蛋白、P5 3mRNA与PCNA表达呈明显正相关。结论 PCNA、P5 3基因异常与幼年性息肉病不典型增生的形成有关 ,P5 3基因参与诱导细胞增殖。

Abstract:

Objective Juvenile polyposis syndrome (JPS) may present epithelial dysplasia, while the molecular mechanism of dysplasia has not been explained. This paper aims to study its pathologic mechanisms by detecting the expressions of proliferating cell muclear antigen (PCNA), P53 protein (DO-7), P21 wafl and P53 mRNA in JPS cases with dysplasia. Methods Thirty-five specimens from 5 cases with JPS (24 specimens with dysplasia and 11 without dysplasia), 5 normal specimens from colonic mucosa, 32 specimens from simple JP and 10 specimens from colorectal cancer were collected. The expressions of PCNA, P53 protein (DO-7) and P21 waf1 were detected by immunohistochemistry. The expression of P53 mRNA was detected using in situ hybridization techniques. Results The average PCNA labelling index, the positive expressions of P53 protein and P53 mRNA, and the positive expression areas of P53 in JPS cases with dysplasia were significantly higher than those in JPS cases without dysplasia. There was no significant difference in the positive expression rate of P21 waf1 between them. The expressions of P53 protein and P53 mRNA were positively correlated with PCNA expression in JPS cases with dysplasia. Conclusions PCNA and the variation of P53 gene may be involved in the formation of dysplasia. The genetic changes of P53 might play an important role in the induction of cell proliferation.