LOSS OF INTERLEUKIN-4 RECEPTOR-ASSOCIATED MOLECULE GP200-MR6 IN HUMANBREAST-CANCER - PROGNOSTIC-SIGNIFICANCE

Several in vitro studies stress a potentially important role of interl eukin 4 (IL-4) and the related gp200-MR6 molecule in the immunological response to cancer and in tumour proliferation. In the present study, we assessed the expression of gp200-MR6 in primary breast cacrinomas using the MR6 monoclonal antibody. Results were correlated with tumour parameters (T-,N-stage, histology, grade, oestrogen and epidermal gro wth factor (EGF) receptors), and the impact on survival was assessed. Twenty-four out of 110 cases (22%) were positive for gp200-MR6, 62 out of 110 (56%) expressed weak staining and 24 out of 114 (22%) did not stain. The normal breast epithelia were invariably stained for gp200-M R6 showing that down-regulation or loss of this molecule occurred duri ng the evolution of breast cancer. Gp200-MR6 loss was independent from differentiation, nodal positivity and oestrogen receptor levels as we ll as patients' age. Loss of the gp200-MR6 molecule was more frequent in lobular cases (P=0.03). The overall survival was better, although n ot reaching statistical significance, in patients with positive gp200- MR6 expression (92% alive at 5 years compared with 70% for those with weak or no expression, P=0.1). The local relapse-free survival was ind ependent of gp200-MR6 status. It is concluded that loss of gp200-MR6 m ay be one of the mechanisms through which breast cancer cells escape i mmune surveillance, resulting in an increased metastatic potential and poorer outcome. Evidence of down-regulation of the gp200-MR6 molecule has implications for IL-il-linked toxin therapy and, as IL-4 is an in hibitor of breast epithelial growth, may represent loss of a tumour-su ppression mechanism.