title: Overexpression of c-myc is associated with adverse clinical features and worse overall survival in multiple myeloma.
abstract: The role of c-myc in multiple myeloma (MM) is controversial. We conducted a retrospective study of 117 patients with MM diagnosed between 2004 and 2010 at Herlev Hospital. Immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) were performed on tissue microarrays (TMAs) made from diagnostic bone marrow aspirates. Clinical data were obtained from the Danish Multiple Myeloma Database (DMMD). Overexpression of c-myc was found in 40% of patients. MYC translocation was found in 10% of patients. Overexpression of c-myc was not associated with MYC translocation. Overexpression of c-myc was associated with hypercalcemia (p = 0.02) and extramedullary myeloma (p < 0.01). Overexpression of c-myc was associated with shorter overall survival (OS) by multivariable analysis of the entire patient cohort [HR 1.92 (1.06-3.45), p = 0.03] and univariable analysis of high-dose-therapy (HDT)-ineligible patients [HR 2.01 (1.05-3.86), p = 0.04]. Further studies of c-myc overexpression in larger cohorts of patients with MM are warranted.
authors.affiliation: a Department of Pathology , Copenhagen University Hospital Herlev , Herlev , Denmark ;
authors.forename: Agoston Gyula
authors.initials: AG
authors.lastname: Szabo
authors.affiliation: b Department of Hematology , Copenhagen University Hospital Herlev , Herlev , Denmark.
authors.forename: Anne Ortved
authors.initials: AO
authors.lastname: Gang
authors.affiliation: a Department of Pathology , Copenhagen University Hospital Herlev , Herlev , Denmark ;
authors.forename: Mette Ølgod
authors.initials: MØ
authors.lastname: Pedersen
authors.affiliation: a Department of Pathology , Copenhagen University Hospital Herlev , Herlev , Denmark ;
authors.forename: Tim Svenstrup
authors.initials: TS
authors.lastname: Poulsen
authors.affiliation: b Department of Hematology , Copenhagen University Hospital Herlev , Herlev , Denmark.
authors.forename: Tobias Wirenfeldt
authors.initials: TW
authors.lastname: Klausen
authors.affiliation: a Department of Pathology , Copenhagen University Hospital Herlev , Herlev , Denmark ;
authors.forename: Peter
authors.initials: P
authors.lastname: Nørgaard
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D003131:Combined Modality Therapy; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality* / Q000628:therapy; D009367:Neoplasm Staging; D011379:Prognosis; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics* / Q000378:metabolism; D015203:Reproducibility of Results; D012189:Retrospective Studies; D014178:Translocation, Genetic; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc
keywords: Genes; multiple myeloma; myc; prognosis; proto-oncogene proteins c-myc; therapeutics