Article

Cancer Immunity, Vol. 8, p. 2 (1 February 2008) Submitted: 5 September 2007. Accepted: 8 October 2007.

Prognostic impact of cancer/testis antigen expression in advanced stage multiple myeloma patients

Valéria C. C. Andrade1, André L. Vettore2,3, Roberta S. Felix1, Manuella S. S. Almeida1, Fabrício de Carvalho1, José Salvador R. de Oliveira1, Maria de Lourdes Lopes Ferrari Chauffaille1, Adagmar Andriolo4, Otavia L. Caballero5, Marco Antonio Zago6 and Gisele W. B. Colleoni1

1Discipline of Hematology and Hemotherapy, Universidade Federal de São Paulo, UNIFESP, São Paulo, Brazil

2Ludwig Institute for Cancer Research, São Paulo Branch, Brazil

3Universidade Federal de São Paulo, UNIFESP, Diadema, Brazil

4Laboratory Medicine Department, Universidade Federal de São Paulo, UNIFESP, São Paulo, Brazil

5Ludwig Institute for Cancer Research, New York Branch, USA

6Faculdade de Medicina de Ribeirão Preto/USP, Brazil

Communicated by: LJ Old

Keywords: human, multiple myeloma, CT antigens, mRNA, tissue distribution, prognosis

Abstract

This study aims to analyze the expression of 14 cancer/testis (CT) antigens in multiple myeloma (MM) to identify possible prognostic markers and therapeutic targets. The expression of MAGEA1, MAGEA2, MAGEA3/6, MAGEA4, MAGEA10, MAGEA12, BAGE1, MAGEC1/CT7, the GAGE family, LAGE-1, PRAME, NY-ESO-1, SPA17 and SSX1 was studied by RT-PCR in 15 normal tissues, a pool of 10 normal bone marrow samples, 3 normal tonsils and bone marrow aspirates from 6 normal donors, 3 monoclonal gammopathies of undetermined significance (MGUS), 5 solitary plasmacytomas, 39 MM samples (95% advanced stage) and the MM cell line U266. MAGEC1/CT7 was expressed in bone marrow aspirates from one MGUS and one plasmacytoma. The frequencies at which CT antigen were found to be expressed in MM patients were MAGEC1/CT7 77%, LAGE-1 49%, MAGEA3/6 41%, MAGEA2 36%, GAGE family 33%, NY-ESO-1 33%, BAGE-1 28%, MAGEA1 26%, PRAME 23%, SSX-1 26%, MAGEA12 20.5%, MAGEA4 0%, and MAGEA10 0%. Cox's regression model showed that GAGE family expression and having >6 CT antigens expressed were independent prognostic factors when all patients were analyzed. However, MAGEC1/CT7 expression was the only independent prognostic factor when non-transplanted patients where analyzed. Based on our findings, MAGEC1/CT7, MAGEA3/6 and LAGE-1 are good candidates for immunotherapy, since together they cover 85% of our MM cases. Furthermore, expression of the GAGE family, >6 CT antigens and MAGEC1/CT7 seem to have impact on MM prognosis.