Prognostic Values Of Novel Molecules In NF-κB Pathway Among Peripheral T Cell Lymphoma And Diffuse Large B Cell Lymphoma

BACKGROUND AND PURPOSE:The peripheral T cell lymphomas(PTCLs) are a group of heterogeneous aggressive non-Hodgkin’s lymphomas(NHLs) associated with poor outcome. Currently there is no standard treatment available for these diseases. Searching for new biomarkers is of great importance for unveiling its mechanism and investigating new drugs. Diffuse large B cell lymphoma(DLBCL) is the most common type of NHLs. Although outcome in DLBCL has improved with the introduction of Rituximab, a few patients are still refractory to standard therapy or endure an early relapse of disease. These patients cannot be recognized since lack of sensitive prognostic markers. Recently, many high-output genome-wide studies have proved that NF-kB pathway is a potential oncogenic pathway in PTCL and DLBCL. Deregulated molecules in NF-kB pathway have become cutting-edge in this field. Our study aim to screen a variety of molecules in NF-kB pathway for their prognostic values that can be used for risk stratification and individualized therapy.METHODS:This retrospective study included previously untreated patients diagnosed with DLBCL or PTCL in the pathology system at Peking Union Medical College Hospital from January2007to December2012. Formalin-fixed, paraffin-embedded blocks of these patients were collected. Tissue microarray was built in a subset of specimens. Expression of NIK, BTRC, MYD88, CARD11, TNFAIP3and Ki-67was examined immunohistochemically. Subtype of DLBCL was determined by Hans algorithm(CD10, BCL6, MUM1). The pattern of NIK, BTRC, CARD11, MYD88and TNFAIP3was further studied and their correlation with outcome was analyzed.RESULTS:Our study included58patients with PTCL and79patients with DLBCL. Two reactive lymph nodes were used as control. In PTCL, the positive rate for NIK, BTRC, MYD88, CARD11, TNFAIP3was10.53%,33.3%,73.68%,92.73%,42.68%, respectively. NIK was associated with PTCL subtypes(P=0.048), ECOG(P=0.045) and dosage of chemotherapy(P=0.009). MYD88was associated with ECOG(P=0.05) while CARD11was associated with PTCL subtype(P=0.02). The patient with positive NIK expression had a poorer overall survival(OS) rate when compared with negative NIK expression(2-yr OS16.67%VS26.25%, P<0.001). Multivariant analysis further confirmed that NIK, along with ECOG and dosage of chemotherapy, was an independent predictor of OS. In DLBCL, the positive rate for NIK, BTRC, MYD88, CARD11, TNFAIP3was32.43%%,57.69%,60.53%,65.33%,31.65%, respectively. Apart from the association between TNFAIP3and primary site(P=0.018), other molecules showed no significant associations with patient characteristics. Positive CARD11expression was associated with a inferior EFS(2-yr EFS52.03%VS86.12%, P=0.036). Even in patients with a high IPI(3-5points), this difference still remained significant(Median EFS not reached VS557days, P=0.0332). B symptoms(P=0.016) and non-responsive treatment(P=0.001) were independent prognostic factor for the EFS in DLBCL.CONCLUSIONS:In PTCL, patient with a positive expression of NIK had a shorter OS when compared with a negative NIK. NIK was an independent predictor of the prognosis. In DLBCL, CARD11positive patients had a shorter EFS compared with negative CARD11. This differences remained significant when patients were in high IPI(3-5points). TNFAIP3, MYD88, BTRC had no impact on survival in PTCL or DLBCL.