Expression And Correlation Of Deficient Mismatch Repair、PD-1and PD-L1 In Breast Cancer

Objective:Mismatch repair deficiency,PD-1 and PD-L1 expression were examined in different molecular subtypes of invasive breast cancer to explore the relationship between the three and different molecular subtypes and clinicopathological characteristics of invasive breast cancer,and to analyze the correlation between the three.Methods:Archived paraffin samples from 102 patients with surgically resected primary invasive breast cancer from January 2018 to December 2020 in the breast Department of the first hospital of Shanxi Medical University were collected,and clinicopathological data such as age and menstrual status of the corresponding patients were reviewed and recorded.Breast cancer was classified into 4 subtypes according to the guidelines,including luminal A type in 26 cases,luminal B type in 22 cases,HER-2 overexpression type in 27 cases,and triple negative type in 27 cases.Mismatch repair deficiency,PD-1and PD-L1 expression was assessed by immunohistochemistry in samples to investigate the relationship between the three and different molecular subtypes of invasive breast cancer and clinicopathological data,and to analyze the correlation between the three.Statistical analysis was performed using SPSS 23.0,and comparisons between groups were analyzed byχ~2test or continuity correctedχ~2test,using Spearman’s rank correlation analysis for correlations between mismatch repair deficiency,PD-1,and PD-L1,with P<0.05 considered statistically significant.Results:1.Mismatch repair deficiency positive was found in 23.5%of 102 primary invasive breast cancers.The positive ratios in luminal A,luminal B,HER-2 overexpressing and triple negative breast cancer(TNBC)were 19.2%,27.3%,18.5%and 29.6%,respectively,and there was no significant difference in the expression of mismatch repair deficiency among different subtypes(P>0.05).The expression of mismatch repair deficiency was significantly associated with patient age and lymph node metastasis(P<0.05),but not with menstrual status,tumor diameter,histological grade,er,PR and HER-2 expression(P>0.05).2.PD-1 positivity was found in 29.4%of 102 primary invasive breast cancers.Their positive rates were statistically significant(P<0.05)in different molecular subtypes of breast cancer:15.4%in luminal A,13.6%in luminal B,37.0%in HER-2 overexpressing and 48.1%in triple negative breast cancer(TNBC).PD-1 expression was significantly associated with lymph node metastasis,tumor diameter,ER and PR expression in patients(P<0.05),but not with menstrual status,age,histological grade and HER-2expression(P>0.05).3.PD-L1 positivity was found in 33.4%of 102 primary invasive breast cancers.Their positive rates were statistically significant(P<0.05)in different molecular subtypes of breast cancer:15.4%in luminal A,18.2%in luminal B,40.7%in HER-2overexpressing and 55.6%in triple negative breast cancer(TNBC).PD-L1 expression was strongly correlated with lymph node metastasis,tumor diameter,histological grade,ER and PR expression in patients(P<0.05),but not with menstrual status,age or HER-2expression(P>0.05).4.Mismatch repair deficiency was neither correlated with PD-1 expression(r=0.048,P=0.634)nor PD-L1 expression(r=0.147,P=0.140).A positive correlation was observed between PD-1 and PD-L1 expression(r=0.274,P=0.005).Conclusion:1.The expression of mismatch repair deficiency was significantly associated with a lower age of onset,presence of axillary lymph node metastasis(P<0.05),suggesting that breast cancer patients who developed mismatch repair deficiency may have a worse prognosis than those with intact mismatch repair.2.There were differences in the expression levels of PD-1 and PD-L1 among different subtypes of invasive breast cancer(P<0.05),and both of them were more highly expressed in TNBC,suggesting that TNBC patients are more likely to obtain efficacy from immune checkpoint inhibitors than other subtypes.3.The expression of PD-1 and PD-L1 was closely associated with larger tumor diameter and presence of lymph node metastasis(P<0.05),suggesting that elimination of immune escape from tumors using PD-1/PD-L1 inhibitors may improve the treatment outcome and improve survival of patients with PD-1,pd-l1-positive breast cancer.4.PD-1 is positively correlated with PD-L1 expression,and the simultaneous detection of the two proteins in breast cancer patients or help to pick out the benefit population from anti immune checkpoint therap.