| ObjectiveTo investigate the relationship between the expression of PD-1/PD-L1 and clinicopathological features,molecular subtypes,interstitial infiltration and prognosis of breast carcinomas before and after neoadjuvant chemotherapy(NAC),and whether PD-1 and PD-L1 in breast carcinomas before and after neoadjuvant chemotherapy exist a correlation with the prognosis of breast carcinomas,whether PD-1 and PD-L1 can be an important factor in the detection of breast carcinoma prognosis and whether or not PD-1 or(and)PD-L1 immunotherapy can be used for the treatment of breast carcinomas,it is important to provide some clinical evidence.Methods90 cases of primary invasive ductal carcinoma of the breast were collected in Lanzhou General Hospital of People's Liberation Army(PLA)from June 2008 to November 2011,ranging in age from 29 to 66 years.Forty-eight patients underwent chemotherapy with AC-T(Anthracyclines,nitrogen mustard sequential taxane drugs)and 34 patients underwent FAC-T(Antipyrimidines,anthracyclines,nitrogen mustards sequential taxane drugs),3 patients received platinum-based chemotherapy and 5 patients received Herceptin plus-dose chemotherapy.The clinical pathological features and prognosis of breast cancer patients receiving neoadjuvant chemotherapy were statistically analyzed.PD-I and PD-L1 immunohistochemical staining were performed on the samples of patients before and after chemotherapy to investigate the relationship between PD-1 and PD-L1 in breast carcinomas and its interstitial infiltration of lymphocytes and in different molecular subtypes of breast carcinomas expression differences and in different subtypes of breast carcinomas expression.In addition,patients were followed up for their survival.ResultsPART ONE1.Before chemotherapy,there was a significant correlation between the expression of PD-1 and PD-L1 in breast carcinomas and the stage before chemotherapy,lymph node metastasis,progesterone receptor expression,nipple and skin involvement,and calcification(P<0.05).There was no statistically significant correlation between age,tumor diameter,visit time,family history,menstrual status,estrogen receptor and human epidermal growth factor 2(P>0.05).After chemotherapy,the expression of PD-1 and PD-L1 in breast carcinomas was significantly correlated with tumor size,staging after chemotherapy,lymph node metastasis,and progesterone receptor expression(P<0.05),There was no significant correlation between skin and nipple involvement,family history,menstrual status,estrogen receptor,human epidermal growth factor 2 expression,calcification age,and visit time(P>0.05).2.The expression of PD-1 and PD-L1 before chemotherapy in different subtypes of breast carcinomas patients was no statistically significant(P>0.05).There was no statistically significant correlation between PD-1 expression in different subtype breast carcinomas patients after chemotherapy(P>0.05),and there was a statistically significant correlation between PD-L1 expression in different subtype breast carcinomas patients(P=0.036).PART TWO1.The positive expression rates of PD-1 in breast carcinomas before and after neoadjuvant chemotherapy were 62.2%(56/90)and 43.3%(39/90)respectively.There was a significant difference in the expression of PD-1 in breast cancer before and after chemotherapy(P=0.012);The positive rate of PD-L1 expression in breast carcinomas before and after neoadjuvant chemotherapy was 63.3%(57/90)and 64.4%(58/90)respectively;there was no significantly statistical difference in the expression of PD-L1 in breast cancer before and after chemotherapy(P-0.876).2.The expression of PD-1 in breast carcinomas before and after neoadjuvant chemotherapy was significantly correlated with the patient's 3-year and 5-year PFS and OS in patients(P?0.001).The expression of PD-L1 in breast carcinomas before and after neoadjuvant chemotherapy was correlated with the patient's 5-year PFS.The correlation was not statistically significant(P=0.078;P=0,066).The 5-year OS correlation was statistically significant(P=0.021;P=0.011).There was a significant correlation between the 3-year PFS and OS.(P?0.001);3.Patients with positive expression of PD-1 and PD-L1 before and after neoadjuvant chemotherapy showed significant differences in prognosis compared with the negative.(P<0.01).PART THREE1.The expression of PD-1 and PD-L1 in breast carcinomas stromal infiltrating lymphocytes(sTIL)before chemotherapy was significantly correlated with pre-chemotherapy staging,lymph node metastasis and human epidermal growth factor 2(P<0.05).There was no significant difference(P>0.05)between age,tumor diameter,visit time,nipple and skin involvement,family history,menstrual status,estrogen receptor,progesterone receptor,and calcification.The expression of PD-1 and PD-L1 in breast carcinomas interstitial infiltrating lymphocytes(sTIL)after chemotherapy was significantly associated with the visit time and staging after chemotherapy(P<0.05),but with age,tumor diameter,and lymph nodes.There was no significant difference in metastasis,skin and nipple involvement,family history,menstrual status,estrogen receptor,progesterone receptor,human epidermal growth factor 2 expression and calcification(P>0.05).2.The positive expression rate of PD-1 in breast carcinomas and mesenchymal infiltrating lymphocytes before and after neoadjuvant chemotherapy was 40.0%(36/90)and 42.2%(38/90)respectively;PD-1 positive cells in the interstitial infiltrating lymphocytes of breast carcinomas before and after neoadjuvant chemotherapy The positive expression rate of PD-L1 was 42.2%(41/90)and 56.7%(50/90)respectively.Before and after neoadjuvant chemotherapy,PD-1 and PD-L1 were expressed in different subtypes of breast carcinomas interstitial infiltrating lymphocytes(sTIL).The difference was not statistically significant(P>0.05).3.Before and after neoadjuvant chemotherapy for breast carcinomas,the correlation between PD-1,PD-L1 and the expression of PD-1 and PD-L1 in the interstitial infiltrating lymphocytes(sTIL)of breast carcinomas was statistically significant(P<0.01).4.The expression of PD-1 and PD-L1 in breast carcinomas interstitial infiltrating lymphocytes(sTIL)before and after neoadjuvant chemotherapy was significantly associated with the 3-year and 5-year PFS and OS(P<0.01).5.Before and after neoadjuvant chemotherapy,the positive expression of PD-1 and PD-L1 in patients with breast carcinomas interstitial infiltrating lymphocytes(sTIL)was significantly different from that of patients with negative expression(P<0.01).Conclusion1.PD-1,PD-L1 expression in breast carcinomas and its interstitial lymphocytes before and after neoadjuvant chemotherapy,its expression and breast carcinomas diameter,clinical stage,lymph node metastasis,PR,HER-2,with or without The clinical pathological features such as calcification are related,and PD-1 and PD-L1 can be used as indicators of the invasiveness and metastasis of breast carcinomas.2.The expression of PD-1 and PD-L1 in breast carcinomas is related to the expression of infiltrating lymphocytes in the interstitium,indicating that the expression of PD-1 and PD-L1 in breast carcinomas may also be affected by interstitial infiltration.The influence of PD-1 and PD-L1 expression in lymphocytes suggests that in the tumor microenvironment,interstitial infiltrating lymphocytes may also be involved in tumor recurrence and metastasis.3.The expression of PD-1 is significantly different before and after neoadjuvant chemotherapy in breast carcinomas.However,the expression of PD-1 and PD-L1 in the interstitial infiltrating lymphocytes before and after chemotherapy is different but not statistically significant.The above phenomenon indicates that chemotherapy can not only change the breast carcinomas.The expression of PD-1 and PD-L1 in cancer tissues can also affect the expression of PD-1 and PD-L1 in the microenvironment around breast carcinomas.4.The expression of PD-1 and PD-L1 before and after chemotherapy is significantly related to the prognosis of breast carcinomas patients.The prognosis of PD-1 and PD-L1 positive patients is worse than that of negative patients,indicating that PD-1 and PD-L1 are expected to be indicators of prognosis of breast carcinomas. |
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