Frequency and Prognostic Relevance of Cancer Testis Antigen 45 Expression in Multiple Myeloma

Abstract

Introduction: Cancer testis (CT) antigens have become the most extensively studied antigen group in the field of tumor immunology. CT45 antigen expression was described in colon adenocarcinomas, germ cell tumors, Hodgkin's lymphomas and, more recently, in multiple myeloma (MM).Aims: This study aims to analyze the expression of CT45 in normal tissues and in plasma cell disorders and to identify possible associations with clinical data and prognosis in MM.Patients and Methods: The expression of CT45 was studied in twenty normal tissues (testis, placenta, skeletal muscle, bladder, lung, spleen, heart, brain, fetal brain, thymus, uterus, stomach, mammary gland, pancreas, prostate, small intestine, kidney, adrenal gland, spinal cord, colon and one pool of ten normal bone marrow samples) and in bone marrow aspirates from three monoclonal gammopathies of undetermined significance (MGUS), five solitary plasmacytomas, 61 newly diagnosed MM patients and MM cell line U266 by RT-PCR.Results:CT45 was positive in three out of 20 (15%) normal tissues tested: lung, brain (both fetal and adult) and spinal cord. Among monoclonal gammopathies, CT45 was positive in two out of five (40%) solitary plasmacytomas' bone marrow aspirates, 10 out of 61 (16%) MM bone marrow aspirates and in the U266 MM cell line. Six out of 10 (60%) CT45 positive MM cases were classified as International Staging System (ISS) 3 (p = 0.009). Six CT45-positive cases were classified as plasmacytic (PC) and four as polymorphic (PM). Median OS of the MM group was 21 months. Nine patients were submitted to autologous stem cell transplantation. All of the transplanted cases were CT45-negative. Univariate analysis showed that Durie-Salmon Staging System (Durie-Salmon IIIA: N = 35, median OS = 40 months; Durie-Salmon IIIB: N = 19, median OS = 12 months; log-rank p= 0.0139), b2microglobulin (b2microglobulin £ 5.5 mg/L: N = 27, median OS = 40 months; b2microglobulin > 5.5 mg/L: N = 24, median OS = 12 months, log-rank p= 0.0520, Breslow p = 0.0352, Tarone-Ware p = 0.0399), plasma cell morphology (PC: N = 38, median OS = not reached; PM: N = 11, median OS = 12 months; PB: N = 5, median OS = 1 month; log-rank p= 0.0037), transplantation proceedings (transplanted patients: N = 9, median OS = not reached; non-transplanted patients: N = 47, median OS = 14 months; p = 0.0064) and CT45 expression (CT45 expression negative: N = 46, median OS = 25 months; CT45 expression positive: N = 10, median OS = 3 months, log-rank p = 0.038 for all patients and CT45 expression negative: N = 37, median OS = 19 months; CT45 expression positive: N = 10, median OS = 3 months, p = 0.0245, only non-transplanted patients) had impact on OS. Cox Regression Model showed that only plasma cell morphology (p = 0.029, RR 5.288, CI 1.77704–15.7988), transplant proceedings (p = 0.0742, RR 0.1582, CI 0.0209–1.1976) and CT45 expression (p = 0.0016, RR 7.0403, CI2.0978–23.6278) were independent prognostic factors in MM patients survival. CT45-positive cases were associated with poor outcome and presented 7 times more chance of worse evolution then the negative ones.Conclusions:CT45 was expressed in only 16% of MM patients. However, we demonstrated for the first time that positive expression of CT45 was associated with high ISS scores and poor outcome in MM