title: P53 expression correlates with poorer survival and augments the negative prognostic effect of MYC rearrangement, expression or concurrent MYC/BCL2 expression in diffuse large B-cell lymphoma.
abstract: In patients with diffuse large B-cell lymphoma, MYC rearrangement (MYC-R), MYC expression, or concurrent expression of MYC and BCL2 is associated with a poorer prognosis. P53 expression also has been shown to confer inferior survival in diffuse large B-cell lymphoma patients, but less is known about the role of P53 expression in those with MYC-R, MYC expression (MYC+), or MYC&BCL2 co-expression (MYC+/BCL2+). We studied P53 expression in 201 patients with untreated de novo diffuse large B-cell lymphoma. Sixty-seven (33%) cases were P53 positive, 56 (28%) had MYC-R (including 17 MYC/BCL2 double hit lymphoma), 86 (45%) were MYC+/BCL2+, and 47 (24%) were positive for both MYC and P53. Compared with patients with P53 negative lymphoma, the P53 positive group had a poorer overall survival (P=0.004). In patients with lymphoma harboring MYC-R, MYC expression or MYC+/BCL2+, P53 expression was associated with a significantly worse overall survival (P<0.0001, P=0.01, and P=0.035, respectively). Patients with lymphoma showing concurrent P53 expression and MYC-R had a worse prognosis compared with patients with either P53 expression or MYC-R alone (P<0.0001). Similarly, P53 enhanced the negative prognostic effect of MYC expression in DLBCL patients. In addition, among patients with lymphoma with concurrent MYC and P53 expression, MYC and BCL2 or BCL2 & P53 expression, those patients with tumors with MYC and P53 expression had the worst overall survival (P=0.005), regardless of BCL2 expression status. Multivariate analysis demonstrated that both MYC-R and P53 expression were independent prognostic factors in this patient cohort. In conclusion, our data suggest that P53 expression and MYC -R or MYC expression have an additive negative prognostic effect in diffuse large B-cell lymphoma patients. Assessment of P53 expression adds additional prognostic information in de novo diffuse large B-cell lymphoma patients, especially in subgroups with MYC-R, MYC expression and MYC and BCL2 double expression.
authors.affiliation: Pathology, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: Xuan J
authors.initials: XJ
authors.lastname: Wang
authors.affiliation: Department of Hematopathology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
authors.lastname: L Jeffrey Medeiros
authors.affiliation: Department of Hematopathology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Bueso-Ramos
authors.affiliation: Department of Hematopathology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Guilin
authors.initials: G
authors.lastname: Tang
authors.affiliation: Department of Hematopathology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Sa
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Lymphoma & Myeloma, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Oki
authors.affiliation: Department of Hematopathology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Parth
authors.initials: P
authors.lastname: Desai
authors.affiliation: Department of Hematopathology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Khoury
authors.affiliation: Department of Hematopathology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Roberto N
authors.initials: RN
authors.lastname: Miranda
authors.affiliation: Department of Hematopathology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Zhenya
authors.initials: Z
authors.lastname: Tang
authors.affiliation: Hematology/Oncology, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: Nishitha
authors.initials: N
authors.lastname: Reddy
authors.affiliation: Department of Hematopathology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Shaoying
authors.initials: S
authors.lastname: Li
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000627:therapeutic use; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000627:therapeutic use; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000627:therapeutic use; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D014750:Vincristine / Q000627:therapeutic use; D055815:Young Adult
chemical_list: C000595707:BCL2 protein, human; C489427:MYC protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc; D016159:Tumor Suppressor Protein p53; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone