Expression Of E-Cadherin In Lymphoproliferative Diseases

BackgroundE-cadherin（E-cad）is a transmembrane glycoprotein with a molecular weight of120k D.It is a member of the classical cadherin family and also a cell adhesion molecule.It is distributed on the cell surface and the junction between cells,and has been proved to play an important role in embryonic development and the homeostasis of the adult internal environment.The loss of its expression can lead to the destruction of cell junction,and the loss of its expression in tumor tissue indicates that the prognosis of tumor is poor,and the probability of invasion and metastasis of tumor cells is high^[1-3].Plasmaid dendritic cells are a subgroup of dendritic cells with plasma cell like morphology and abundant endoplasmic reticulum,which usually exist in lymphoid organs,such as lymph nodes and tonsils.The characteristic is the secretion of large amounts of interferon I（IFN-I）and other pro-inflammatory cytokines in the context of autoimmune diseases or viral infections,promoting innate and acquired immune responses^[4,5].A recent study showed that E-cad has strong and consistent expression in cases of mother cell plasma like dendritic cell tumors involving the skin,and confirmed that malignant p DCs tumor cells weaken IFN-I signal through E-cad expression and signal transduction,resulting in poor tumor immunemicroenvironment[6].E-cad is a recognized marker of epithelial cells in the pathological community,expressed in the glandular epithelium of tissues and organs such as the skin,esophagus,stomach,intestines,and gallbladder.It is also a marker for various epithelial derived cancer cells,widely expressed in various tumor tissues of various systems.E-cad is commonly used in clinical diagnosis for differential diagnosis of adenocarcinoma and mesothelioma,breast ductal cancer,and breast lobular cancer.The tumors with the highest E-cad loss rate include Merkel cell carcinoma,undifferentiated thyroid carcinoma,breast lobular carcinoma,and sarcomatoid carcinoma.They typically have morphological features of dedifferentiation,loss of adhesion,and poorer clinical prognosis.However,there is relatively little research on the expression of E-cad in lymphatic tissues.Some studies have shown that lymphatic tissues sometimes exhibit weak staining,but it is not clear which type of cell they are expressed in.Luisa Lorenzi et al.demonstrated through double staining that most p DCs in reactive lymph nodes and tonsils were E-cad positive,while p DCs scattered in normal bone marrow were E-cad negative^[7].In lymphohematological diseases,Eike Burandt et al.’s tissue chip study only included 38 cases of Hodgkin’s lymphoma and 39 cases of non Hodgkin’s lymphoma,without further classification.The results showed that the expression rate of E-cad in Hodgkin’s lymphoma was 26.3%（10/38）,while in non Hodgkin’s lymphoma it was 0^[7].Wang Liangzhe et al.showed that the positive expression rate of E-cad in plasma cell myeloma（MM）was 46.34%,and the overall survival rate of E-cad negative patients was lower than that of E-cad positive patients.The homophilic interaction between E-cad positive myeloma cells and p DCs has been shown to induce TLR9degradation and then inhibit the production of IFN-I by p DCs^[8-10].Aims1.The expression intensity and rate of E-cadherin in various lymphoproliferative diseases,and its value in daily diagnosis of lymphohematopoietic tumors.2.Compare the labeling of plasma like dendritic cells by E-cadherin and CD123,observe the distribution and intensity of p DC in different diseases,and reveal its role in the occurrence and development of lymphoproliferative diseases.MethodsThis study collected 13 common lymphomas and 4 reactive lymphoid tissue diseases from the Pathology Department of the Second Affiliated Hospital of Guangzhou Medical University since 2018.The tissues of 5 normal bone marrow and5 reactive lymph nodes were used as controls,and E-cadherin and CD123 staining were performed on the tissues of these cases.Two pathologists conducted double-blind film review to determine four expression intensities based on staining intensity and the proportion of stained cells in the tissue.Dyeing intensity（i）:0 points for no staining,1 point for yellow,2 points for brownish yellow,and 3 points for brownish brown.Immunohistochemical score（total score of 300 points）=∑（PI×I）=（percentage of yellow cells）×1)+（percentage of brown cells）×2)+（percentage of brown cells）×3)。Expression intensity:negative（score<10 points）,weakly positive（10 points≤score<30 points）,moderately positive（30 points≤score<60points）,strongly positive（score≥60 points）.Record the immunohistochemical scores of E-cad and CD123 in each case,and compare the expression of E-cad and CD123 in lymphoproliferative diseases between different types and within the same species.Results1.E-cadherin was positively expressed in three groups of cases of lymphoid tissue reactive disease,mature B-cell lymphoma,and mature T-cell lymphoma in the experiment.The staining localization was consistent with CD123,and the staining intensity was higher in most cases than CD123.It can be used as a supplementary term for staining of plasma like dendritic cells.2.The plasma like dendritic cells labeled by E-cadherin and CD123 are always distributed in the paracortical area and closely related to the high endothelial vein,which is consistent with the premise that plasma like dendritic cells migrate to the T cell rich area of lymphatic tissue through the high endothelial vein.Plasma like dendritic cells are often distributed around the necrotic area of the lesion,and around multinucleatedgiant cells.In peripheral lymphoma,they can be banded along the marginal zone.3.The number and distribution of plasma like dendritic cells vary among various lymphoid tissue proliferative diseases.In the three diagnostic groups of the experiment,the positive rate and histochemical score of E-cadherin in the lymphoid tissue reactive disease group were higher than those in the mature B-cell lymphoma group and mature T-cell lymphoma group（the difference was statistically significant）,while there was no statistically significant difference between the mature B-cell lymphoma group and the mature T-cell lymphoma group.This may be due to the increased recruitment of E-cad labeled plasma like dendritic cells in the context of infection and autoimmune factors.4.The diagnosis of more E-cad expression in this experiment includes Castleman disease,histicytic necrotizing lymphadenitis,classic Hodgkin lymphoma,angioimmune T-cell lymphoma and NK/T-cell lymphoma.The pathogenesis of these reactive lesions or parts of lymphoma is unknown,but almost all are associated with viral infection and autoimmune status,and histologically often show a mixed pattern of inflammatory cell infiltration.5.CD123 marked the vascular endothelium in all cases of follicular lymphoma and individual diffuse large B-cell lymphoma and classic Hodgkin lymphoma,while the corresponding E-cad only marked pulp dendritic cells.ResultE-cadherin is expressed in various lymphoid tissue proliferative diseases such as lymphoid tissue reactive diseases and mature B/T cell lymphoma,usually in plasma like dendritic cells.It needs to be differentiated from poorly differentiated cancer cells to avoid misdiagnosis.The pathogenesis of these reactive lesions or lymphoma is not yet clear,but almost all are related to viral infection and autoimmune status.Histologically,they often exhibit a mixed inflammatory cell infiltration pattern,and plasma like dendritic cells are recruited by inflammatory mediators to release IFN-Ⅰand participate in immune responses.Different diseases have the number and distribution pattern of plasma like dendritic cells.Usually,plasma like dendritic cells are distributed near the high endothelial veins in the subcortical area,around the necrotic area of the lesion,and around multinucleated giant cells.In marginal zone lymphoma,they can be distributed in a ribbon along the marginal zone.Our experiment has broadened the research on the expression profile of E-Cad in lymphoid tissue diseases,but lymphoproliferative diseases are a vast system.We hope to conduct E-Cad staining on more disease types,cases,and more systematic subtypes in the future to observe more patterns.