TP53 Mutation and Complex Karyotype Portends a Dismal Prognosis in Patients With Mantle Cell Lymphoma

Clin Lymphoma Myeloma Leuk. 2018 Nov;18(11):762-768. doi: 10.1016/j.clml.2018.07.282. Epub 2018 Aug 23.

Abstract

Background: TP53 mutation (TP53mut) and a complex karyotype (CK) were shown to be predictors of poor outcome in mantle-cell lymphoma (MCL). In this study we examined the combined effect of both of these risk factors.

Patients and methods: Patients diagnosed with MCL between January 2000 and December 2014 (n = 74) were evaluated. Forty-eight of them had available material for TP53 and cytogenetic examination. We analyzed the prognostic effect of combined TP53mut and CK in the cohort of patients treated with rituximab-containing therapy.

Results: Three-year (3-y) overall survival (OS) and 3-y progression-free survival (PFS) in CK patients were shorter compared with non-CK (P = .001 for OS; P = .02 for PFS). TP53mut was a predictor of shorter survival compared with TP53 wild type (OS and PFS; P < .001). The incidence of TP53mut was not significantly associated with CK (P = .240). CK and TP53mut were predictors of inferior PFS and OS independent of age and Mantle-Cell Lymphoma International Prognostic Index, with hazard ratios of 2.35 (P = .024), 4.50 (P < .001) for PFS and 4.31 (P < .001), 5.46 (P < .001) for OS analysis in the CK and TP53mut groups, respectively. The combination of TP53mut and CK status stratified the patients into 3 prognostic groups (P < .001) with the worst outcome in patients with CK and TP53mut.

Conclusion: TP53 mutation and CK occurred independently and patients harboring both had a dismal prognosis. The study suggests the importance of molecular cytogenetics and examination of the TP53mut status to be performed simultaneously before treatment.

Keywords: Cytogenetics; Morphology; Next-generation sequencing; Prognosis; Stratification.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / genetics*
  • Chromosome Aberrations*
  • Cohort Studies
  • Female
  • Follow-Up Studies
  • Humans
  • Karyotype
  • Lymphoma, Mantle-Cell / drug therapy
  • Lymphoma, Mantle-Cell / genetics
  • Lymphoma, Mantle-Cell / pathology*
  • Male
  • Middle Aged
  • Mutation*
  • Prognosis
  • Survival Rate
  • Tumor Suppressor Protein p53 / genetics*

Substances

  • Biomarkers, Tumor
  • TP53 protein, human
  • Tumor Suppressor Protein p53