Expression Of PD-1/PD-L1 And Its Clinical Significance In Esophageal Squamous Cell Carcinoma

Objective: To observe the expression of programmed death-1 and its ligand programmed death ligand-1 in esophageal squamous cell carcinoma tissues,and to investigate their clinical significance.Method: A total of 90 patients received radical esophagectomy at the fourth hospital of Hebei Medical University between January 2011 to August2011 and lymphadenectomy number no less than 12 were involved in this study.Immunohistochemical method was used to detect the positive expression of PD-1 and PD-L1.They were divided into 0 point(negative expression),one point(positive rate was between 1%~5%)and two point(positive rate >5%),respectively.According to the sum score of PD-1and PD-L1,no expression group(the score was 0),low risk expression group(the score was between 1 and 2)and intermediate/high risk expression group(the score was between 3 and 4)were generated.SPSS 21.0 statistical software was used to analyze the relationship between expression of PD-1,PD-L1,different expression groups and clinicopathologic features and prognosis in patients with esophageal squamous cell carcinoma,and multivariate analysis was also conducted.Results:1 Expression of PD-1 and PD-L1 in esophageal squamous cell carcinoma:It was shown that the positive expression of PD-1 and PD-L1 were 17.8%(16/90)and 30.0%(27/90),respectively.14 cases were co-expressed,and 61 cases showed none expressed.PD-L1 expression in esophageal squamous cell carcinoma tissues had a significant positive correlation with PD-1expression(χ2=30.275,P=0.000).2 Relationship between PD-1,PD-L1,level of combined expression and clinicopathological features: Univariate analysis showed that none of thepositive expression of PD-1 and PD-L1 was correlated with gender,location and length of the tumor,T stage,tumor differentiation and blood vessel invasion.The positive expression of PD-1 and PD-L1 in <60 years old group was significantly higher than those in ≥ 60 years old group(31.7% versus 6.1%,χ2=9.996,P=0.002;46.3% versus 16.3%,χ2=9.576,P=0.002).And the positive expression of PD-1 and PD-L1 in lymph node metastasis group was significantly higher than those in lymph node metastasis negative group(26.1% versus 9.1%,χ2=4.444,P=0.035;41.3% versus 18.2%,χ2=5.726,P=0.017).The positive expression rate of PD-1 and PD-L1 in stage Ⅰ were both 7.7%.While in stage Ⅱ was 8.3% and 22.2%,respectively.And 29.3%,43.9% in stage Ⅲ,respectively.There were significantly difference between each group(χ2=6.805,P=0.033;χ2=7.891,P=0.019).The level of combined expression had a significant correlation with age,lymph node metastasis,tumor differentiation and pTNM stage(χ2=16.111,P=0.00;χ2=8.663,P=0.013;χ2=6.619,P=0.037;χ2=10.879,P=0.028).3 Relationship between PD-1,PD-L1,level of combined expression and prognosis: The median overall survival(OS)in the whole group was 49.7months,and the median progression-free survival(PFS)was 27.5 months.There was no significant difference between PD-1 positive and negative expression groups in OS and PFS(χ2=1.768,P=0.184;χ2=2.221,P=0.136).The 1-,3-,5-year OS and PFS in PD-L1 positive expression group was 68.0%,36.0%,32.0% and 57.7%,30.8%,30.8%,respectively,significantly lower than 89.3%,62.5%,53.6% and 85.7%,53.6%,50.0% in negative expression group(χ2=5.579,P=0.018;χ2=5.565,P=0.018).The level of combined expression had a significant correlation with OS and PFS(χ2=10.238,P=0.006;χ2=9.625,P=0.008).Age,T stage,lymph node metastasis,p TNM stage,tumor differentiation,vascular invasion,PD-1 expression,PD-L1 expression,combined expression and postoperative adjuvant therapy were all included in multivariate COX regression analysis.It showed that postoperative adjuvant therapy was an independent risk factor for postoperative OS(P=0.015),while lymph node metastasis was an independent risk factor for postoperative OSand PFS(P=0.000;P=0.001).Conclusion: In esophageal squamous cell carcinoma tissues,there is a significant positive correlation between PD-1 and PD-L1 expression.The positive expression rate of PD-1 and PD-L1 in patients with lymph node metastasis and advanced pTNM stage are relatively higher,and both of them are negatively correlated with age.The positive expression of PD-1 has no correlation with OS and PFS,while patients with PD-L1 positive expression have poor prognosis.Postoperative adjuvant therapy is an independent risk factor for postoperative OS,while lymph node metastasis is an independent risk factor for postoperative OS and PFS in esophageal squamous cell carcinoma patients.