title: High expression of REV7 is an independent prognostic indicator in patients with diffuse large B-cell lymphoma treated with rituximab.
abstract: REV7 is a multifunctional protein involved in DNA damage tolerance, cell-cycle regulation, gene expression, and carcinogenesis. Although its expression is reportedly associated with poor prognosis in human solid tissue cancers, the significance of REV7 expression in hematopoietic malignancies is unclear. This study evaluated the prognostic significance of REV7 expression in patients with diffuse large B-cell lymphoma (DLBCL) treated with rituximab-combined chemotherapy. Using immunohistochemistry, we analyzed 83 specimens of de novo DLBCL [38 germinal center B-cell-like (GCB) and 45 non-GCB DLBCLs] treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone for REV7 expression. Aberrant REV7 expression was detected in DLBCL cell nuclei. High REV7 expression was associated with significantly shorter overall survival (OS) and progression-free survival (PFS) using Kaplan-Meier analysis and log-rank tests (P < 0.01 and P < 0.01, respectively). Multivariate analysis revealed that REV7 expression is an independent prognostic factor for both OS and PFS. Additionally, when patients were divided into four groups using a combination of REV7 expression and international prognostic index (IPI) or Bcl-2 expression, REV7(High)/IPI(Poor) and REV7(High)/Bcl-2(High) patients showed the poorest outcome. These results indicate that REV7 may be a useful biomarker to predict the prognosis of patients with DLBCL treated with rituximab.
authors.affiliation: Department of Pathology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan.|Department of Hematology, Kitasato University School of Medicine, Sagamihara, Japan.
authors.forename: Sosei
authors.initials: S
authors.lastname: Okina
authors.affiliation: Department of Pathology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Yanagisawa
authors.affiliation: Department of Pathology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan.|Department of Hematology, Kitasato University School of Medicine, Sagamihara, Japan.
authors.forename: Maki
authors.initials: M
authors.lastname: Yokoyama
authors.affiliation: Department of Pathology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan.
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Sakurai
authors.affiliation: Department of Pathology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Numata
authors.affiliation: Department of Pathology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Umezawa
authors.affiliation: Department of Hematology, Kitasato University School of Medicine, Sagamihara, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Higashihara
authors.affiliation: Department of Pathology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan. murakumo@med.kitasato-u.ac.jp.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Murakumo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000032:analysis; D005260:Female; D015870:Gene Expression; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D064246:Mad2 Proteins / Q000032:analysis* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000032:analysis / Q000235:genetics; D009713:Nucleotidyltransferases / Q000032:analysis / Q000235:genetics; D011379:Prognosis; D012189:Retrospective Studies; D000069283:Rituximab / Q000627:therapeutic use*; D015996:Survival Rate; D055815:Young Adult; D000099270:Y-Family DNA Polymerases
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D064246:Mad2 Proteins; D009687:Nuclear Proteins; D009713:Nucleotidyltransferases; D000069283:Rituximab; C120552:MAD2L2 protein, human; C429004:REV1 protein, human; D000099270:Y-Family DNA Polymerases
keywords: Diffuse large B-cell lymphoma; Immunohistochemistry; Prognosis; REV7; Rituximab