非小细胞肺癌中抑癌基因PTEN表达、突变与肿瘤发生发展及预后的相关性研究

PTEN Mutation and Expression in Non-Small Cell Lung Cancer

目的通过检测非小细胞肺癌(NSCLC)中PTEN基因的表达及突变,进一步阐明PTEN基因与NSCLC发生发展及预后的关系。方法收集有完整随访资料的61例NSCLC蜡块,用免疫组化SP法检测PTEN蛋白的表达;选择其中30例癌组织蜡块提取DNA,PCR扩增PTEN基因第3、5、7、8外显子,并进行DNA测序。结果 PTEN蛋白表达在NSCLC组织中低于癌旁正常组织;并随着临床分期的增加及出现淋巴结转移而降低;PTEN蛋白阳性组的生存期明显高于阴性组,而与年龄及肿瘤的分化程度无关。仅1例标本发生了PTEN基因外显子5、7、8的纯和性丢失,2例发现了2类突变位点的存在,这2类突变均位于内含子中。结论 PTEN蛋白的表达水平下调在NSCLC的发生发展中可能起了重要作用;而PTEN基因的改变比率远远低于其蛋白表达下调的程度。

Objective To clarify the relationship between PTEN and the tumorigenesis,progression or prognosis of non-small cell lung cancer （NSCLC）.Methods Expression of PTEN was examined in 61 cases of NSCLC and 20 cases of normal lung tissue by SP immunohistochemistry.Exon 3,5,7,9 of PTEN gene were evaluated by PCR and sequencing.Results PTEN expression was lower in NSCLC than in control.PTEN expression was correlated with lymph node metastasis,clinical stage and overall survival,but not with patient’s age,sex and histological grading.One of 30 cases showed loss of homozygosity of PTEN exon 5,7 and 8 in NSCLC and 2 showed mutations of PTEN.Conclusion Down-regulation of PTEN protein might be involved in the development of NSCLC pathogenesis.However,the genetic alterations of PTEN were infrequent.