| Objective:Immune checkpoint inhibitors play an important role in the treatment of Mismatch Repair Defects(dMMR)solid tumors.CD 155(Differentiation Cluster 155)is one of the immune checkpoints and has a synergistic effect with PD-L1.At present,there is no literature report about the study of CD 155 in endometrial cancer.This study examined the expression of CD 155 in endometrial cancer tissues,and explored the relationship between CD 155 and endometrial cancer clinicopathological data and MMR protein.Methods:1.Collected 114 cancer tissues from patients with endometrial cancer who had undergone gynecological surgery in Yunnan Provincial Cancer Hospital,the Third Affiliated Hospital of Kunming Medical University from December 2017 to February 2019.2.The expression of MMR protein(MLH1,MSH2,MSH6,PMS2)and CD155 in 114 endometrial cancer tissues were detected by immunohistochemistry3.Collect relevant clinical and pathological data of patients,use SPSS software to explore the clinical significance of MMR and CD 155 in endometrial cancer,and analyze the correlation between CD 155 and MMR protein expression.Results:1.Expression of MMR protein and CD155 protein in endometrial cancerImmunohistochemical results showed that among 114 endometrial cancer patients,the expression loss rates of MMR,MLH1,PMS2,MSH2 and MSH6 were 40.35%,25.44%,24.56%,6.14%and 5.26%,respectively.There were 23 cases(20.18%)with strong CD155 expression,70 cases(61.40%)with positive expression,and 21 cases(18.42%)with negative expression.2.Correlation between MMR protein and CD155 protein of endometrial cancer and age of diseaseIn terms of age,the average age of patients with missing MMR expression was 54.03 ± 7.31 years old,and the average age of patients with normal MMR expression was 51.46 ± 8.76 years.Obvious statistical significance(P<0.01).No significant statistical significance was found between the CD 155 expression negative,positive and strong positive groups and the age of disease(P>0.05).3.Correlation between MMR protein and CD155 protein and high-risk factors in endometrial cancerIn 114 patients with endometrial cancer,the loss of MMR protein expression was related to the menopausal age and BMI.The average age of menopause in the dMMR group was significantly greater than that in the Mismatch Repair Complete(pMMR)group.The average age of menopause was 50.21 ± 4.52 years old and 48.17 ±4.81 years old,the difference was statistically significant(P<0.01).The average BMI of patients in pMMR group and dMMR group was 24.96 ± 4.42kg/m2 and 24.04± 3.78kg/m2,respectively.The average BMI of patients in pMMR group was significantly greater than that in dMMR group,and the difference was statistically significant(P<0.01).The lack of MMR expression and patients with high-risk factors such as medical diseases,family history of tumors,and maternal history have no significant statistical significance(P>0.05).CD 155 expression and high-risk factors such as age at menopause,BMI,comorbid medical diseases,family history of tumor and pregnancy and delivery history were not significantly statistically significant(P>0.05).4.Correlation between MMR protein and CD155 protein in endometrial cancer tissue and clinical pathological factors of patientsAnalysis of MMR protein and CD 155 protein and clinical pathological factors of patients revealed that MMR protein expression was correlated with tumor diameter,and the expression loss rate of MMR protein in endometrial cancer with tumor diameter<2cm and? 2cm was 32.61%and 67.39%,respectively.There was a statistical difference(P=0.046).The CD155 protein expression rate is higher in G3(low differentiation),FIGO(Federation International of Gynecology and Obstetrics)?-?,lymph node metastasis,and involvement of the lower uterine group than G1/G2(high/medium differentiation),FIGO ?-?,The patients with no lymph node metastasis and uninvolved lower uterine group had statistically significant differences(P<0.05).CD155 protein expression was not significantly statistically significant in tissue type,tumor diameter,LVSI,and depth of myometrial invasion in patients with endometrial cancer(P>0.05)Subgroup analysis showed that among 37 patients with FIGO stage ?-?endometrial cancer,dMMR patients had a higher proportion of tumor diameter>2 cm(47.62%vs 81.25%),and the difference was statistically significant(P=0.048).Analysis of statistical results of 77 cases of FIGO stage ?-? endometrial cancer showed that MMR protein in patients with early endometrial cancer in the high-risk group(muscle layer infiltration?1/2 and/or tumor diameter?2cm and/or G3)The deletion rate was higher than that in the low-risk group(muscle layer infiltration depth<1/2,tumor diameter<2cm,G1/2),and the difference had a certain statistical trend(P=0.062).The expression of MMR protein was not statistically significant in the early endometrial cancer tissue type,tissue differentiation,tumor diameter,depth of myometrial invasion and involvement of the lower uterus(P>0.05).CD 155 is associated with lower uterine involvement.Compared with patients with lower uterine involvement,the positive and strong positive rates of CD 155 in early endometrial cancer patients with lower uterine involvement are increased(5.56%vs 41.46%vs 33.33%)Significance(P=0.023).5.Correlation between the expression of CD155 protein and MMR protein in endometrial cancerChi-square test or Fishers exact probability test analysis showed that there was no statistically significant difference between the expression of CD155 and the lack of MMR expression(P>0.05).6.Correlation between MMR protein and CD155 protein of endometrial cancer tissue and ER,PR and Ki67 of patientsThe expression of MMR and CD155 and the expression of ER,PR and Ki67 were not statistically significant(P>0.05).7.Correlation between MMR protein and CD155 protein of endometrial cancer tissue and circulating immunity of patientsAnalysis of the relationship between MMR protein expression and the number of circulating immune factors and lymphocytes in endometrial cancer patients showed that MMR protein expression was associated with peripheral blood IFN?(interferon y),IL10(interleukin 10),IL2(interleukin 2),IL4(interleukin 4),IL6(interleukin 6),TNFa(tumor necrosis factor)has nothing to do(P>0.05).MMR expression and Th cell effector T cells,CD4+/CD8+,CD45+CD3+,CIK(NK cell-like T lymphocytes)and NK(natural killer cells)did not show significant statistical significance(P>0.05).In terms of immunity,CD 155 belongs to the cell adhesion molecule of the Ig superfamily.Analysis of circulating immune factors revealed that there was no significant statistical significance in the expression of CD 155 and the expression of IFN?,IL10,IL2,IL4,IL6,and TNF ? in peripheral blood(P>0.05).Compared with CD155-negative patients,the expression of circulating Th cells in CD155(+)group was increased(P=0.041)in CD155-positive patients,which was not related to the expression of effector T cells,CD4+/CD8+,CD45+CD3+,CIK and NK(P>0.05).8.Correlation between endometrial cancer tissues ER,PR and Ki67 and clinicopathologyFurther analysis of the clinical characteristics of ER,PR,Ki67 and endometrial cancer found that Ki67 seems to be correlated with endometrial cancer tissue type,tissue differentiation,LVSI,and involvement of the lower uterine segment.The expression of Ki67 in patients with endometrioid adenocarcinoma was higher than that in patients with non-endometrioid adenocarcinoma(74.07%vs 25.93%),the difference was statistically significant(P=0.003).Compared with G1/G2 endometrial cancer patients,Ki67 had a higher positive rate in G3 patients(46.15%vs 12%),the difference was statistically significant(P<0.01).The positive expression rate of Ki67 in LVSI+patients was higher(50%vs 19.39%),and the difference was statistically significant(P=0.011).The positive rate of Ki67 was 36,59%in patients with lower uterine involvement and 16.44%in patients without uterine involvement,the difference was statistically significant(P=0.027).The positive expression rate of Ki67 in patients with lymph node metastasis was significantly higher than that in patients without lymph node metastasis(40%vs 18.46%),with a certain statistical trend(P=0.055).PR is related to the involvement of the lower uterus.The proportion of PR+patients with lower uterine involvement is lower than that of patients without uterine involvement,and the difference is statistically significant(P=0.038).9.Correlation between endometrial carcinoma CD155 combined with Ki67 and clinicopathologyCD 155 combined with Ki67 protein is related to endometrial cancer tissue differentiation and lower uterine involvement,statistical results show that compared with CD155-Ki67-and CD155+Ki67-or CD155-Ki67+ patients,the proportion of CD 155+Ki67+in G3 and lower uterine involvement patients Higher,the difference was statistically significant(P<0.01).10 Case report10.1 Double primary cancerIn this study,there were 3 cases of dual primary cancer,of which 1 case was endometrial cancer with breast cancer,1 case was endometrial cancer with rectal cancer,1 case was endometrial cancer with colon cancer,MMR protein immune group The results showed that MLH1,PMS2,MSH2 and MSH6 were all positive,including 2 cases of gastrointestinal endoscopy.10.2 Patients with a family history of tumor MMR expressionNine patients had a family history of tumors,of which 4 had missing MMR protein expression,2 had missing MLH1/PMS2 expression,1 had missing MLH1/MSH2 expression,and 1 had missing MSH6 expression.10.3 MMR expression in patients with disease in gastrointestinal endoscopyThe gastroscopy results of 5 patients showed gastric abnormalities,and the results of enteroscopy of 20 patients showed abnormalities.The gastroscopy and enteroscopy of 4 patients showed abnormalities.19 patients(65.52%)had normal MMR expression and 10 patients(34.48%)had missing MMR expression There were 4 cases of MLH1/PSM2 expression loss,1 case of MLH1/MSH2 expression loss,2 cases of MSH2 expression loss,2 cases of MSH6 expression loss,and 1 case of PSH2 expression loss.[Conclusion]1.Our research shows that dMMR is closely related to the age of endometrial cancer,late menopause,small BMI,and tumor diameter?2cm.2.The positive expression of CD 155 is closely related to the poor degree of tumor tissue differentiation,late FIGO stage,lymph node metastasis and involvement of the lower uterine segment.CD155 may play an important role in the progression and metastasis of endometrial cancer.3.CD 155 expression affects Th cell expression in patients with endometrial cancer,and CD155 has nothing to do with MMR expression status.4.The positive expression rate of CD 155 combined with Ki67 in G3 and the lower part of the uterine body increased significantly.CD 155 combined with Ki67 may be used as a biological predictor for poor prognosis. |
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