title: MAGE-C1/CT-7 expression in plasma cell myeloma: sub-cellular localization impacts on clinical outcome.
abstract: Plasma cell myelomas (PMs) have a poor prognosis. Cancer-testis (CT) antigens are immunogenic proteins, representing potential targets for tumor vaccination strategies. The expression of the CT antigens GAGE, MAGE-A4, MAGE-C1/CT-7, and NY-ESO-1 was investigated on paraffin-embedded bone marrow biopsies from 219 PM and 8 monoclonal gammopathy of undetermined significance (MGUS) patients. The frequency and prognostic impact of these CT antigens were compared with known morphological prognostic markers (i.e. Mib1 labeling index) and the presence of the translocations t(4;14)(p16.3; q32) and t(11;14)(q13;q32). We show that MAGE-C1/CT-7 is the most prevalent CT antigen, expressed in 57% of PMs in a high percentage of tumor cells. While MAGE-C1/CT-7 was absent in non-malignant plasma cells, plasma cells of patients with MGUS did express MAGE-C1/CT-7, but no other CT antigens. MAGE-C1/CT-7 was more frequently expressed in PMs with an elevated proliferation rate (Mib1 >10%) compared to PMs with a low proliferation rate (Mib1 <or=10%, 71%versus 29%, P < 0.001) and correlated with overall survival, depending on its subcellular distribution. PMs with pure cytoplasmic MAGE-C1/CT-7 expression showed a better prognosis (48 months versus 33 months, P < 0.05) than PMs with combined nuclear-cytoplasmic or nuclear expression only. Thus, expression of MAGE-C1/CT-7 in patients with monoclonal gammopathies represents a predictor of outcome and overt malignant transformation.
authors.affiliation: Institute of Surgical Pathology, Department of Pathology, University Hospital Zurich, Zurich, Switzerland. Marianne.Tinguely@usz.ch
authors.forename: M
authors.initials: M
authors.lastname: Tinguely
authors.forename: B
authors.initials: B
authors.lastname: Jenni
authors.forename: A
authors.initials: A
authors.lastname: Knights
authors.forename: B
authors.initials: B
authors.lastname: Lopes
authors.forename: D
authors.initials: D
authors.lastname: Korol
authors.forename: V
authors.initials: V
authors.lastname: Rousson
authors.forename: A
authors.initials: A
authors.lastname: Curioni Fontecedro
authors.forename: S B
authors.initials: SB
authors.lastname: Cogliatti
authors.forename: A G
authors.initials: AG
authors.lastname: Bittermann
authors.forename: U
authors.initials: U
authors.lastname: Schmid
authors.forename: C
authors.initials: C
authors.lastname: Dommann-Scherrer
authors.forename: R
authors.initials: R
authors.lastname: Maurer
authors.forename: C
authors.initials: C
authors.lastname: Renner
authors.forename: N M
authors.initials: NM
authors.lastname: Probst-Hensch
authors.forename: H
authors.initials: H
authors.lastname: Moch
authors.forename: A
authors.initials: A
authors.lastname: Knuth
authors.forename: A
authors.initials: A
authors.lastname: Zippelius
mesh_terms: D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000032:analysis*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000175:diagnosis* / Q000401:mortality* / Q000473:pathology; D009363:Neoplasm Proteins / Q000032:analysis*; D011379:Prognosis; D016019:Survival Analysis
chemical_list: D000951:Antigens, Neoplasm; C473332:CT7 antigen, human; C110905:MAGEC1 protein, human; D009363:Neoplasm Proteins