非小细胞肺癌中神经内分泌分化和多药耐药性的关系研究

目的:探讨非小细胞肺癌(NSCLC)中神经内分泌(NE)分化与多药耐药(MDR)的相关性。方法:采用链霉亲和素过氧化酶连接(SP)免疫组化法检测113例NSCLC中神经元特异性烯醇化酶(NSE)、突触素(SYN)和嗜铬素A(CgA)的表达,采用原位分子杂交对同一病例中多药耐药基因(MDR1)和多药耐药相关蛋白(MRP)基因mRNA的表达进行检测,并对相关数据进行统计学处理。结果:①NSCLC中NSE、SYN、CgA的阳性率分别为53.1%,26.6%和6.2%。至少有2种NE标记物表达者有24例(21.2%),其表达与肿瘤的分化程度有关(P<0.05);②MDR1和MRPmRNA在NSCLC组织中的阳性表达率分别为51.3%,80.5%,二者表达与肿瘤组织类型、分化程度、淋巴结转移、TNM分期等无关,二者在NSCLC中的表达存在明显相关(P<0.01);③2种MDR相关基因mRNA在具有NE分化的NSCLC中的表达均较不伴NE分化者为低(P<0.05)。结论:NE分化可能与NSCLC多药耐药性的产生有密切关系。

Relationship Between Neuroendocrine Differentiation and Multidrug Resistance in Non-small Cell Lung Cancer

Objective: To investigate the correlation between neuroendocrine(NE)differentiation and multidrug resistance (MDR) in (non-small cell lung cancer, NSCLC). Methods: The expression of NSE,SYN and CgA were measured by immunohistochemistry. In situ hybridization was used to detect MDR1 and MRP gene. The results were checked with χ 2 test. Results: ① The positive rates of the NE markers were 53.1%, 26.6% and 6.2% for NSE, SYN and CgArespectively, and 21.2% for at least two markers positively expressed. The expression of at least two markers was associated with the degree of differentiation (P<0.05). ② Fifty-eight cases (51.3%) were MDR1 mRNA-positive and nighty-one cases (80.5%) were MRP mRNA-positive respectively. The expression of MDR1 mRNA and MRP mRNA was not related to histological subtypes, cell differentiation, TNM stages and lymphatic metastasis. There was a significant correlation between expression of MDR1 mRNA and MRP mRNA in NSCLC (P<0.01). ③ The expression of the two MDR associated genes in the positive group for at least two markers was significantly lower than that in the negative one (P<0.05). Conclusion: There may be a close relationship between NE differentiation and MDR in NSCLC.