|Table of Contents|

PD-L1 and MDM2 expression in non-small cell lung cancer patients harboring rare EGFR mutation and their role in survival

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2023 06
Page:
1061-1068
Research Field:
Publishing date:

Info

Title:
PD-L1 and MDM2 expression in non-small cell lung cancer patients harboring rare EGFR mutation and their role in survival
Author(s):
LUAN Feiyang1; NIU Wenxia2; WU Yinying1; FAN Yangwei1; SHI Yu1; DONG Danfeng1; DONG Xuyuan1
1.Department of Medical Oncology，First Affiliated Hospital of Xi'an Jiaotong Univiersity，Shaanxi Xi'an 710061，China;2.Department of Internal Medicine,Xiang'an Affiliated Hospital of Xiamen Univiersity,Fujian Xiamen 361106,China.
Keywords:
non-small cell lung cancer; EGFR rare mutation; overall survival
PACS:
R734.2
DOI:
10.3969/j.issn.1672-4992.2023.06.015
Abstract:
Objective:To investigate the expression of PD-L1 and MDM2 in non-small cell lung cancer (NSCLC) patients with rare mutations of epidermal growth factor receptor (EGFR),analyze their relationship with clinicopathological characteristics and prognosis,and explore the prognostic factors of rare mutations of EGFR and the application prospect of immunotherapy.Methods:69 patients with rare EGFR mutation were enrolled (from January 2010 to 2017) for this study.IHC was used to assess the expression of PD-L1,MDM2 in 51 NSCLC patients formalin fixed paraffin embedded tissues.Nine para-carcinoma tissues and 8 normal tissues were regarded as control group.The relationship between PD-L1,MDM2 expression,clinicopathological characteristics with overall survival of NSCLC patients with rare EGFR mutation were analysed.Results:There were 64 NSCLC patients with rare EGFR mutation.41 patients (64.06%) harbored single rare mutation,and the other 23 patients (35.94%) harbored complex mutations.The median neutrophil-lymphocyte ratio (NLR) was 2.63，PD-L1 was positively expressed in 29.41% tumor tissues,and was negatively expressed in para-carcinoma tissues and normal tissues.MDM2 was positively expressed in 86.27% tumor tissues,33.33% para-carcinoma tissues and 12.5% normal tissues,respectively.PD-L1 expression level in stage I/II patients were higher than that of stage III/IV (P=0.013),and MDM2 expression level in stage III/IV patients were higher than that of stage I/II（P=0.001）.Expressions levels of PD-L1 and MDM2 had no statistically significant difference among different age,gender,smoking,NLR level,complex mutation and pathological grade (P>0.05).The median overall survival time of 64 NSCLC patients with rare EGFR mutation was 22.31 months.Clinicopathological characteristics,such as age,gender,smoking,complex mutations,PD-L1 expression and MDM2 expression had no influence on patients' overall survival.Median OS (46.16 months) of patients with NLR<2.63 was longer than that of patients with NLR≥2.63 (12.58 months)(χ2=9.72,P=0.002).Tumor pathological grade 1/2 showed a superior mOS than grade 3 patients (41.46 months vs 15.97 months）（χ2=6.17，P=0.013）.Patients with stage I/II showed longer mOS than patients with stage III/IV (59.17 months vs 15.97 months）（χ2=18.89，P=0.000）.The stage (HR=8.778，P=0.000) and NLR level (HR=2.667,P=0.007) were independent factors which affected the prognosis of NSCLC patients with rare EGFR mutation.Conclusion:NLR may serve as a prognosis factor for NSCLC patients with rare EGFR mutation.The positive expression rate of PD-L1 is high in NSCLC with rare EGFR mutation,which may benifit from immunotherapy.

References:

［1］CHEN WQ,ZHENG RS,BAADE PD,et al.Cancer statistics in China,2015［J］.Ca Cancer J Clin,2016,66(2):115-132.
［2］HERBST RS,HEYMACH JV,LIPPMAN SM.Lung cancer［J］.New England Journal of Medicine,2008,359(13):1367-1380.
［3］RUSSO A,FRANCHINAT,RICCIARD G,et al.Heterogeneous responses to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in patients with uncommon EGFR mutations:New insights and future perspectives in this complex clinical scenario［J］.Int J Mol Sci，2019，20(6):1431.
［4］MORGILLO F,DELLA CC,FASANO M,et al.Mechanisms of resistance to EGFR-targeted drugs:lung cancer［J］.Esmo Open,2016,1(3):e000060.
［5］KEAM B,KIM DW,JIN HP,et al.Rare and complex mutations of epidermal growth factor receptor,and efficacy of tyrosine kinase inhibitor in patients with non-small cell lung cancer［J］.International Journal of Clinical Oncology,2014,19(4):594-600.
［6］LOHINAI Z,HODA MA,FABIAN K,et al.Distinct epidemiology and clinical consequence of classic versus rare EGFR mutations in lung adenocarcinoma［J］.Journal of Thoracic Oncology Official Publication of the International Association for the Study of Lung Cancer,2015,10(5):738-746.
［7］BAEK JH,SUN J,MIM YJ,et al.Efficacy of EGFR tyrosine kinase inhibitors in patients with EGFR-mutated non-small cell lung cancer except both exon 19 deletion and exon 21 L858R:A retrospective analysis in Korea［J］.Lung Cancer,2015,87(2):148-154.
［8］SALEH K,KHALIFESALEH N,HADDAD EE,et al.Negative predictive biomarkers of checkpoint inhibitors in hyper-progressive tumors［J］.Biomarkers in Medicine,2017，11（10）:819-821.
［9］马薇,罗殿中,陈源,等.PD-L1和PD-1在非小细胞肺癌中的表达及其临床意义［J］.实用医学杂志,2011,27(9):1551-1554. MA W,LUO DZ,CHEN Y,et al.Expression and clinical significance of PD-L1 and PD-1 in non-small cell lung cancer［J］.The Journal of Practical Medicine,211,27(9):1551-1554.
［10］AVALLONE G,ROCCABIANCA P,CRIPA L,et al.Histological classification and immunohistochemical evaluation of MDM2 and CDK4 expression in canine liposarcoma［J］.Veterinary Pathology,2016,53(4):773-780.
［11］FREGA S,LORENZI M,FASSAN M,et al.Clinical features and treatment outcome of non-small cell lung cancer (NSCLC) patients with uncommon or complex epidermal growth factor receptor (EGFR) mutations［J］.Oncotarget,2017,8(20):32626-32638.
［12］KEAM B,KIM DW,PARK JH,et al.Rare and complex mutations of epidermal growth factor receptor,and efficacy of tyrosine kinase inhibitor in patients with non-small cell lung cancer［J］.International Journal of Clinical Oncology,2014,19(4):594-600.
［13］MARTIN J,LEHMANN A,KLAUSCHEN F,et al.Clinical impact of rare and compound mutations of epidermal growth factor receptor in patients with non-small-cell lung cancer［J］.Clin Lung Cancer，2019，20(5):350-362.
［14］OZYUREK BA,OZDEMIREL TS,OZDEN SB,et al.Prognostic value of the neutrophil to lymphocyte ratio (NLR) in lung cancer cases［J］.Asian Pacific Journal of Cancer Prevention Apjcp,2017,18(5):1417-1421.
［15］CHEN K,YU X,WANG H,et al.Uncommon mutation types of epidermal growth factor receptor and response to EGFR tyrosine kinase inhibitors in Chinese non-small cell lung cancer patients［J］.Cancer Chemotherapy & Pharmacology,2017,80(6):1179-1187.
［16］FREGA S,LORENZI M,FASSAN M,et al.Clinical features and treatment outcome of non-small cell lung cancer (NSCLC) patients with uncommon or complex epidermal growth factor receptor (EGFR) mutations［J］.Oncotarget,2017,8(20):32626-32638.
［17］KOBAYASHI Y,MITSUDOMI T.Not all epidermal growth factor receptor mutations in lung cancer are created equal:Perspectives for individualized treatment strategy［J］.Cancer Science,2016,107(9):1179-1186.
［18］CHANTHARASAMEE J,POUNGVARIN N,DANCHAIVIJITR P,et al.Clinical outcome of treatment of metastatic non-small cell lung cancer in patients harboring uncommon EGFR mutation［J］.BMC Cancer，2019，19(1):701.
［19］AL-SHIBILI IK,DONNEM T,AL-SAAD S,et al.The prognostic value of intraepithelial and stromal T cells,mast cells and plasma cells in non-small cell lung carcinoma［J］.Virchows Archiv,2009,455:85.

Memo

Memo:
National Natural Science Foundation of China(No.82003287）；国家自然科学基金青年项目(编号:82003287);陕西省自然科学基础研究计划(编号:2020JQ-505);北京希思科临床肿瘤学研究基金会(编号:Y-Q201802-063)
Last Update: 1900-01-01