Expression And Clinical Significance Of TET2 And DNMT3A In Peripheral T Cell Lymphoma

Objective To investigate the expression and clinical and pathological significance of TET2 and DNMT3 A in patients with peripheral T cell lymphoma(PTCL)and the relationship to immunophenotypes of PTCL.Methods 1.Using a series of immunohistochemical markers(CD3,CD4,CD10,BCL-6,CXCL-13,CD30,EMA,ALK),all cases of PTCLs were divided into four groups,including angioimmunoblastic T cell lymphoma(AITL),peripheral T cell lymphoma,not otherwise specified(PTCL-NOS),anaplastic lymphoma kinase negative anaplastic large cell lymphoma(ALK-ALCL)and anaplastic lymphoma kinase positive anaplastic large cell lymphoma(ALK+ALCL).2.The expressions of TET2 and DNMT3 A in 89 cases of PTCL were detected by immunohistochemical analysis.Results 1.89 cases were divide into four subtype,AITL(36 cases,40.44%),PTCL-NOS(26 cases,29.21%),ALK-ALCL(18 cases,20.22%),ALK+ALCL(9 cases,10.11%).2.Both TET2 and DNMT3 A were expressed in cytoplasm and nucleus in PTCL cases.3.Immunohistochemistry staining revealed higher expression of TET2 and DNMT3 A in AITL than that of in PTCL-NOS(P=0.001,P=0.048),ALCL(P=0.001,P=0.001).4.Immunohistochemistry staining revealed higher cytoplasmic expression of TET2 in AITL than that of in PTCL-NOS(P=0.001),ALCL(P<0.001).There also was a higher cytoplasmic expression of DNMT3 A in AITL patients than that with PTCL-NOS(P=0.029),ALCL(P=0.024).5.The nuclear expression of DNMT3 A in patients with AITL was higher than that of PTCL-NOS(P=0.047),and ALCL(P<0.001).6.The expression of TET2 was positively related with that of DNMT3 A in patients with PTCL(r=0.384,P<0.001).The cytoplasmic expression of TET2 was positively related with both cytoplasmic(r=0.350,P=0.001)and nuclear(r=0.365,P<0.001)expression of DNMT3 A in patients with PTCL.7.The expression of TET2 was positively related with that of DNMT3 A in patients with AITL(r=0.478,P=0.003).The cytoplasmic expression of TET2 was positive related with both cytoplasmic(r=0.336,P=0.045)and nuclear(r=0.478,P=0.003)expression of DNMT3 A in patients with AITL.8.The high nuclear expression rate of TET2 in PTCL patients with B symptoms was higher than that in patients without B symptom,the difference was statistically significant(P= 0.003).In patients with stage III + IV,the high cytoplasmic expression rate of TET2 was higher than stage I + II patients,the difference was not statistically significant,but at the critical level(P = 0.061).9.The expression of TET2 and DNMT3 A was not associated with age,sex,LDH level and IPI score and extranodal infiltration in patients with PTCL.Conclusion TET2 and DNMT3 A may be involved in lymphomagenesis of PTCL.TET2 coorperating with DNMT3 A may contribute to the development and progression of PTCL.TET2 combining with DNMT3 A could be used as markers in AITL diagnosis,which could provide new research and strategy for AITL diagnosis and treatment.