【摘要】 目的 分析DLL3、BCL2与LCNEC临床特点的相关性及在不同分子亚型中的表达情况及其临床意义。方法 收集中日友好医院明确诊断肺LCNEC组织标本110例进行临床特点分析，并通过免疫组化方法分析DLL3、BCL2与NE标记物、P53突变、RB1缺失的相关性。结果 DLL3及BCL2的表达与性别无关，更多表达于大于60岁以上且吸烟的患者；DLL3染色阳性(≥1%肿瘤细胞阳性)占比49/110(44.5%),与P53突变型相比，P53野生型中DLL3阳性更具有优势，而P53和RB1共突变型则没有差别，无统计学意义。BCL2染色阳性(≥10%肿瘤细胞阳性)占比72.7%,RB1野生型与突变型患者差异没有统计学意义(P>0.05);与P53野生型相比，BCL2阳性率在P53突变型及P53和RB1共突变型中更具有优势，且有统计学意义。DLL3/BCL2双表达占比35.5%,RB1野生型和RB1突变亚组之间差异无统计学意义(P>0.05),且在P53突变型、P53野生型及P53和RB1共突变型中无明显差别。结论 DLL3及BCL2的表达与性别无关，与年龄及吸烟正相关，P53野生型LCNEC更易在DLL3抑制剂中获益；SCLC样亚型LCNEC患者BCL2抑制剂的获益率更高；除此之外DLL3是LCNEC基于铂类辅助化疗敏感性的预测标志物；免疫组化TTF1阳性或可作为DLL3阳性的替代标记从而提示临床相关的药物治疗选择。更多还原

【Abstract】 Objective To analyze the expression of DLL3 and BCL2 in different molecular subtypes of lung large cell neuroendocrine carcinoma and their clinical significance.Methods The Clinical characteristics of 110 patients with lung LCNEC admitted to China-Japan Friendship Hospital were retrospectively analyzed, and Immunohistochemical analysis the correlation of DLL3 and BCL2 with NE markers, P53 mutation and RB1 deletion.Results The expression of DLL3 and BCL2 was not related to sex, which was strongly associated with smoking in patients over 60 years of age.DLL3 staining positive(≥1% tumor cell positive) accounted for 49/110(44.5%),Compared with P53 mutant, DLL3 positive in P53 wild type was more advantageous, while there was no difference between P53 and RB1 co-mutant, with no statistical significance.BCL2 staining positive(≥10% tumor cells positive) accounted for 72.7%,and there was no difference between RB1 wild type and mutant type(P>0.05).Compared with the wild type of P53,the positive rate of BCL2 was more advantageous in the P53 mutant and the co-mutant of P53 and RB1,and the positive rate was statistically significant.DLL3/BCL2 double expression accounted for 35.5%,and there was no significant difference between RB1 wild type and RB1 mutant subgroup(P>0.05),and no significant difference in P53 mutant, P53 wild type and P53 and RB1 co-mutant.Conclusion The expression of DLL3 and BCL2 was not related to sex, but positively related to age and smoking.P53 wild-type LCNEC is more likely to benefit from DLL3 inhibitors.Patients with SCLC-like subtype LCNEC had a higher rate of benefit from BCL2 inhibitors.In addition, DLL3 is a predictive marker of sensitivity of LCNEC based on platinum-based adjuvant chemotherapy.Immunohistochemical TTF1 positive may serve as a surrogate marker for DLL3 positive, suggesting clinically relevant drug treatment options.更多还原