Abstract
MUC1 is a glycoprotein expressed on the luminal surface of simple epithelia. In carcinoma, MUC1 overexpression is associated with malignancy. In breast cancer patients, increased levels of circulating MUC1 (CA 15.3 tumor marker) are associated with poor prognosis (Tumour Biol.2005; 26:217–20). In myeloma, MUC1 overexpression correlates with apoptosis resistance. We have previously shown (Br J Haematol.2003; 120:344–52) that MUC1 is selectively found in differentiating erythroid cells suggesting a possible role as cross-talk molecule between erythroblasts and bone marrow microenvironment during erythropoiesis. In CD34+ cells cultured in the presence of EPO and SCF, MUC1 is expressed before Glycophorin A (GlyA) during the erythroid differentiation process, and disappears following GlyA up-regulation. Aiming to evaluate the role of MUC1 in the erythroid counterpart present in neoplastic haemopoiesis, we studied MUC1 serum circulating levels in patients affected by Ph-negative Myeloproliferative Chronic Disorders (MPD). We analysed serum samples from 42 MPD patients affected by Polycythemia Vera (PV), Essential Thrombocythemia (ET) and Primary Myelofibrosis (PMF) (N 25, 14, and 3, respectively). CA15.3 (soluble MUC1) levels were determined using the commercially available ADVIA Centaur CA 15.3 assay (Bayer Corporation, NY) and cut off level was set at 25 U/mL. As control group serum samples from healthy donors, matched for sex and age, were also analyzed. Evaluation of the humoral immune response to MUC1 protein core was performed in ELISA. Results indicated that CA15.3 levels were statistically higher in MPD patients than in the control group (p<0.005), this difference was more evident in PV patients (p<0.001) and in female cases (p<0.001). The JAK2V617F mutation status was not associated with CA15.3 values; similarly, neither the clinical or hematological features nor the clinical complications (thrombosis) were influenced byCA15.3 levels. Analysis of the humoral immune response to MUC1 core protein showed no substantial changes in serum anti-MUC1 IgG titers in PV patients, suggesting that in PV increase of soluble MUC1 does not induce immune responses against this self-antigen. Further studies are ongoing to investigate the significance of MUC1 in the development and onset of myeloproliferative disorders. In conclusion, MUC1 levels seem to be increased in PV patients, suggesting that further evaluations on large series of cases should include this test in the diagnostic work-up to PV patients.
Antibody response against HERV-W env surface peptides differentiates multiple sclerosis and neuromyelitis optica spectrum disorder
