Relationship Between Tertiary Lymphoid Structure,Tumor Invasion And Clinicopathological Features In Ductal Carcinoma In Situ Of The Breast

Purpose: To observe the occurrence and structure of tertiary lymphoid structures（TLS）in breast ductal carcinoma in situ（DCIS）,analyze the relationship between TLS and DCIS,DCIS with microinvasion（DCIS-MI）and infiltrating ductal carcinoma（IDC）,and evaluate the significance of TLS in the progression of DCIS tumors.Methods: 103 cases of DCIS,32 cases of DCIS-MI and 78 cases of IDC were collected.The TLS density in cancer foci of DCIS,DCIS-MI and IDC were observed by morphologic and immunohistochemical methods,to evaluate the relationship between TLS and clinicopathologic features of DCIS.Results:1)TLS existed in the form of lymphocyte aggregation in DCIS,DCIS-MI and IDC.TLS was mainly composed of CD20 positive cells,and CD3 positive cells were mostly in the peripheral area of TLS,accompanied by PNAD positive high endothelial veins.BCL-6 positive cells overlapped with CD21 positive follicular dendritic cell network in the germinal center of TLS.TLS was mainly distributed around the tumor ducts in DCIS and DCIS-MI,and at the edge of the invasive focus in IDC.There existed a certain number of early TLS,primary TLS or secondary TLS in DCIS,DCIS-MI and IDC cases.2)The incidence of TLS was 78.6%（81/103）in DCIS,96.9%（31/32）in DCIS-MI,and 66.7%（52/78）in IDC.There was significant difference in the incidence of TLS among the three groups（P<0.001）.3)In DCIS cases,TLS grade was greatly different among different nuclear grade groups（P<0.001）and the group with high nuclear grade had more cases of high-density TLS.The proportion of DCIS-MI with high nuclear grade carcinoma component in the DCIS-MI was 68.8%（22/32）.And TLS density varied among different nuclear grade groups（P =0.007）.And so did TLS densities among different histological grades（P<0.001）,and with or without lymph node metastasis（P=0.043）in IDC patients.4)Different molecular subtypes of both DCIS,DCIS-MI and IDC（P<0.001,P=0.019,P=0.001）also had significantly different TLS densities.The TLS density in HER-2 overexpression subtype was higher than others.5)In DCIS and IDC cases,there was no statistically significant difference in survival between the TLS group and the TLS-free group（P=0.518,P=0.220）.Conclusion: The results of this study show that in DCIS,cancer cells appear high nuclear level,necrosis and HER2 overexpression often accompanied by the formation of TLS,and TLS may be associated with the early infiltration of DCIS,and TLS as a local immune effect structure of cancer may lose its immune monitoring role in early breast cancer.