title: Prognostic impact of p53 aberrations for R-CHOP-treated patients with diffuse large B-cell lymphoma.
abstract: Diffuse large B-cell lymphoma (DLBCL) is the most frequent lymphoma in adults. There are specific alterations that appear repeatedly in DLBCL cases and play a role in lymphomagenesis or progression of the disease. Some aberrations were used as prognostic markers in the pre-rituximab era. Addition of rituximab to the classical anthracycline-based chemotherapy significantly increased the survival rate in DLBCL. Only few prognostic factors have been re-evaluated for patients treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone). We performed complex analysis of the p53 tumor suppressor in collection of 75 DLBCL cases. Fifty-four patients were de novo cases, twenty-one cases developed into DLBCL by transformation from less aggressive disease. We determined functional status by analysis of separated alleles in yeast (FASAY) and analyzed the p53 mutations by cDNA sequencing. We assessed the level of the p53 protein by immunoblot analysis. We used FISH to analyze loss of the p53 and ATM (ataxia telangiectasia mutated) gene deletions. We detected 16 p53 mutations (21.3%) including the mutation activating non-sense-mediated RNA decay pathway. Deletion of the p53 allele was more common in cases with p53 mutation. Mutations and/or deletions of p53 had statistically significant negative impact on progression-free survival and tended to decrease also overall survival in 46 de novo DLBCL patients treated with R-CHOP. p53 aberrations are negative predictors for survival of DLBCL patients treated with R-CHOP.
authors.affiliation: Department of Pathology, University Hospital, 625 00 Brno, Czech Republic.
authors.forename: Lenka
authors.initials: L
authors.lastname: Stefancikova
authors.forename: Mojmir
authors.initials: M
authors.lastname: Moulis
authors.forename: Pavel
authors.initials: P
authors.lastname: Fabian
authors.forename: Ingrid
authors.initials: I
authors.lastname: Vasova
authors.forename: Frantisek
authors.initials: F
authors.lastname: Zedek
authors.forename: Barbora
authors.initials: B
authors.lastname: Ravcukova
authors.forename: Jan
authors.initials: J
authors.lastname: Muzik
authors.forename: Petr
authors.initials: P
authors.lastname: Kuglik
authors.forename: Vladimira
authors.initials: V
authors.lastname: Vranova
authors.forename: Iva
authors.initials: I
authors.lastname: Falkova
authors.forename: Renata
authors.initials: R
authors.lastname: Hrabalkova
authors.forename: Jana
authors.initials: J
authors.lastname: Smardova
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001483:Base Sequence; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000627:therapeutic use*; D004317:Doxorubicin / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056426:Genetic Loci; D006801:Humans; D053208:Kaplan-Meier Estimate; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D011241:Prednisone / Q000008:administration & dosage / Q000627:therapeutic use*; D011379:Prognosis; D000069283:Rituximab; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D014750:Vincristine / Q000008:administration & dosage / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D016159:Tumor Suppressor Protein p53; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone