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 statis-tical significance.BCL2 staining positive(≥10%tumor cells positive)accounted for 72.7%,and there was no differ-ence 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 sig-nificant.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 LC-NEC had a higher rate of benefit from BCL2 inhibitors.In addition,DLL3 is a predictive marker of sensitivity of LC-NEC based on platinum-based adjuvant chemotherapy.Immunohistochemical TTF1 positive may serve as a surrogate marker for DLL3 positive,suggesting clinically relevant drug treatment options.
Large cell neuroendocrine carcinomaMolecular typingDLL3BCL2