title: TNF-α expression in tumor cells as a novel prognostic marker for diffuse large B-cell lymphoma, not otherwise specified.
abstract: Several cytokines promote malignant cell growth and are therefore believed to contribute to disease aggressiveness. The cytokine tumor necrosis factor-α (TNF-α) acts as a tumor-promoting factor and has been linked to all tumorigenic stages in many cancers. Here, we evaluated 62 lymphoma tissue specimens from patients having diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS) by immunostaining with anti-TNF-α antibody. Cytoplasmic TNF-α reactivity in ≥20% of the tumor cells was considered positive. Our results demonstrated that tumor specimens from DLBCL, NOS patients could be divided into 2 types-TNF-α positive (38 cases, 61%) and TNF-α negative (24 cases, 39%)--and that TNF-α positivity in DLBCL, NOS was correlated with poorer overall survival (OS; P=0.0005, log rank test) and progression-free survival (PFS; P=0.0330, log rank test) compared with TNF-α negativity. Cox regression analysis showed that TNF-α expression was a significant prognostic factor for OS (P<0.0001) and PFS (P=0.0323). Regarding OS and PFS, multivariate analysis showed that TNF-α expression in tumor cells was an independent prognostic factor for the International Prognostic Index (IPI). Therefore, TNF-α-positive DLBCL, NOS may constitute a unique subtype of DLBCL, NOS with an aggressive clinical course. The addition of TNF-α expression to the IPI may significantly improve the predictive prognostic value. The therapeutic strategy of DLBCL, NOS patients should be based on correct prognosis; therefore, patients with poor prognoses could be more accurately detected by evaluating both TNF-α expression levels and the IPI.
authors.affiliation: *Department of Internal Medicine (I) †Division of Mathematics ‡Division of Surgical Pathology, Osaka Medical College, Osaka, Japan.
authors.forename: Shoko
authors.initials: S
authors.lastname: Nakayama
authors.forename: Taiji
authors.initials: T
authors.lastname: Yokote
authors.forename: Yuji
authors.initials: Y
authors.lastname: Hirata
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Akioka
authors.forename: Takuji
authors.initials: T
authors.lastname: Miyoshi
authors.forename: Nobuya
authors.initials: N
authors.lastname: Hiraoka
authors.forename: Kazuki
authors.initials: K
authors.lastname: Iwaki
authors.forename: Ayami
authors.initials: A
authors.lastname: Takayama
authors.forename: Uta
authors.initials: U
authors.lastname: Nishiwaki
authors.forename: Yuki
authors.initials: Y
authors.lastname: Masuda
authors.forename: Yasuichiro
authors.initials: Y
authors.lastname: Nishimura
authors.forename: Motomu
authors.initials: M
authors.lastname: Tsuji
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Hanafusa
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D016009:Chi-Square Distribution; D003593:Cytoplasm / Q000276:immunology; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D016403:Lymphoma, Large B-Cell, Diffuse / Q000276:immunology* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012307:Risk Factors; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*
chemical_list: D014408:Biomarkers, Tumor; D014409:Tumor Necrosis Factor-alpha