凋亡调节蛋白Bcl-2家族在非小细胞肺癌中的表达

目的在手术切除的原发性非小细胞肺癌(NSCLC)标本中检测凋亡调节蛋白Bcl-2家族中的Bcl-2、Bax和Mcl-1的表达特征和预后的意义。方法用针对人体的Bcl-2、Bax与Mcl-1的特异性鼠源性抗体采用免疫组化法,检测它们在50例NSCLC患者手术切除的石蜡包埋标本中的表达情况,并结合临床病理分型和追踪预后分析其表达的意义。结果(1)非小细胞性肺癌标本中抗凋亡因子Bcl-2和Mcl-1分别有15例(30%)和29例(58%)表达阳性,有23例(46%)的标本中有促凋亡因子Bax表达阳性。Mcl-1与Bax的表达之间存在正相关(P=0.06)。Bcl-2、Bax和Mcl-1的免疫组化染色以胞浆为主。(2)Mcl-1与Bax在肺癌的不同临床病理分型中没有差异(分别为P>0.250和P>0.900)。(3)Bcl-2的表达与原发性NSCLC手术切除患者总的无复发生存率(P=0.02)和无转移生存率(P<0.01)呈负相关,Mcl-1与Bax的表达与预后无关。结论在NSCLC中,Bcl-2家族蛋白Bcl-2、Mcl-1和Bax的表达等都很常见。Mcl-1的抗凋亡功能可能是通过在蛋白质水平与Bax相互作用形成异二聚体,拮抗Bax的促进凋亡功能而实现的。可能由于它们在凋亡中复杂的相互作用,凋亡调节蛋白Bcl-2家族的表达对NSCLC的临床预后没有直接的影响。

Expression of apoptopsis regulatory proteins of the Bcl-2 family in non-small-cell lung cancer

Objective To investigate the expression features and prognostic significance of apoptopsis regulatory proteins of the Bcl-2family Bcl-2,Bax and Mcl-1in the samples of human primary re-sected non-small-cell lung cancer.Methods We examined the expression of the Bcl-2family pro-teins in50paraffin embedded specimens of pa-tients with resected non -small -cell lung cancer(NSCLC)with murine antibodies specific for the human Bcl-2,Mcl-1and Bax proteins.Their rela-tions to clinical pathological histology and clinical outcome were also comparatively analyzed.Re -sults(1)Tumour cells containing immunostaining for the antiapoptotic proteins Bcl -2and Mcl -1were present in15(30%)and29(58%)of the cas-es evaluated,respectively,whereas immunopositivity for the proapoptotic proteins Bax was found in23(46%)of the samples.The expression of Mcl-1and Bax showed a positive association(P=0.06).The ex-pression of Mcl-1and Bax were not only present in the cytoplasm,they also present in the nucleus.(2)Mcl-1and Bax have no significant difference in different pathological histology in non-small-cell lung cancer(P>0.250and P>0.900respectively).(3)The expression of Bcl-2had a negative influence on overall relapse -free survival and progression -free survival in this population of primary resected NSCLC patients(P=0.02and P<0.01respectedly).The expression of Mcl-1and Bax had no influence on clinical outcome.Conclusions The expression of the Bcl -2family proteins Mcl -1and Bax in NSCLC are frequent.In the protein level,Mcl-1and Bax may form dimmers,thus prevent apoptosis through neutralizing the proapoptotic activity of Bax in malignant cell.Because interactions of the regu-latory factors in apoptosis are complex,Bcl-2family numbers may have no straightforward impact on clinical outcome in this disease.