Expression And Significance Of PD-1 And PD-L1 In Non-Small Cell Lung Cancer In Yunnan Xuanwei Region

[Objective]Study on the expression of PD-1 and PD-L1 in Non-Small Cell Lung Cancer in Yunnan Xuanwei region and research its correlation with the clinicopathological parameters.[Content](1)112 formalin-fixed paraffin embedded(FFPE)samples which have detail medical records during 2014 to 2016 are collected for histologic subtype determination and PCR.Surgical specimens of histologic subtypes according to the WHO classification in 2015 the latest international society for the study of lung cancer,the American thoracic society and European respiratory society(IASLC/ATS/ERS)classification methods to classify.(2)Real-time Fluorescence quantitied PCR is used to detect EGFR,KRAS,EML4-ALK genes mutation.(3)Immunohistochemistry is used to detect PD-1 and PD-L1 expression on protein level.(4)The SPSS 17.0 statistical software is used to analysis the correlation between PD-1,PD-L1 and clinicopathological parameters.[Results](1)62 of 112 NSCLC cases which are from Xuanwei region are EGFR mutated type,including 17 cases with drug-sensitive mutation,45 cases with drug-resistant mutation,and 50 cases with EGFR wild type.10 cases are KRAS mutated type,20 cases are KRAS wild type,KRAS status of 80 cases are unknown.EML4-ALK gene fusion are positive in 3 cases,negative in 20 cases,and unknown in 89 cases.(2)The positive rate of PD-1 expression in TILs and macrophages are 33.9%and 17.0%respectively.The positive rate of PD-L1 expression in TC and TILs are 59.8%and 24.1%respectively.The correlation between PD-1 expression in TILs and PD-L1 expression in TILs has statistical significance(P<0.05).The correlation between PD-1 expression in TILs and PD-L1 expression in TC has no statistical significance(P>0.05).The correlation between PD-1 expression in macrophages and PD-L1 expression in TC and TILs has no statistical significance(P>0.05).(3)PD-1 expression in TILs was only associated with age,the positive rate of PD-1 in TILs of the group which age>60 is higher than that which age<= 60(46.2%vs 26.0%)(P<0.05).There was no statistical significance between the expression of PD-1 in macrophages and clinicopathological partameters(P>0.05).(4)The expression of PD-L1 in TC is associated with clinical stage,lymphnode metastasis,histological type(adenocarcinoma with solid components(P<0.05));No correlation with sex,age,turner size,EGFR and KRAS mutation(P>0.05).Clinical stage is positive-related with PD-L1 positive rate in TC,Stage I,II-IIIa and ?b-? are respectively 44.2%,64.9%and 75.0%.The positive rate of PD-L1 in patiens with lymph node metastasis is significantly higher than that without lymph node metastasis(76%vs 46.8%).In adenocarcinoma,the positive rate of PD-L1 in TC are 11.1%for lepidic predominant adenocarcinoma,45.5%for papillary predominant adenocarcinoma,56.7%for acinar predominant adenocarcinoma,84.4%for solid predominant adenocarcinoma,66.7%for micropapillary predominant adenocarcinoma and 0.0%for mucinous adenocarcinoma.The positive rate of PD-L1 expression in TC with solid components is significantly higher than that without solid components(78.8%vs 41.2%).Statistical results showed that the positive rate of PD-L1 expression in TC is higher in squamous cell carcinoma than adenocarcinoma(71.4%vs58.8%),yet the difference has no statistical significance(P>0.05).Meanwhile,the positive rate of PD-L1 expression in TC of adenocarcinoma with KRAS mutation was higher than that with wild type KRAS(80.0%vs 45.0%),the difference has no statistical significance(P>0.05).Moreover,the correlation between the PD-L1 expression and EML4-ALK fusion has statistical significance in TC(P<0.05).The expression of PD-L1 are all negative in 3 cases of EML4-ALK fusion positive adenocarcinoma cell,and 2 cases are lepidic predominant adenocarcinoma,1 cases is mucous adenocarcinoma.There is no statistical significance between the expression of PD-L1 in TILs and clinicopathological parameters(P>0.05).[Conclusion]1?In Xuanwei region,There is no correlation between the expression of PD-1 in TILs and macrophages and clinical stage,histological type and gene status.2?In Xuanwei region,the expression of PD-L1 in TC is related to clinical stage,lymph node metastasis,histological type of adenocarcinoma and KRAS mutation.The later clinical stage is,the higher positive rate of PD-L1 expression in TC.The positive rate of PD-L1 expression in TC with lymph node metastasis is significantly higher than that without lymph node metastasis.In adenocarcinoma,the positive rate of PD-L1 expression in TC is high in solid predominant adenocarcinoma,while lepidic predominant adenocarcinoma is in a low-level expression,and PD-L1 is hardly expressed in mucinous adenocarcinoma.Furthermore,The positive rate of PD-L1 expression is higher in TC with KRAS mutation than TC with wild type KRAS.