Loss of interleukin 4 receptor-associated molecule gp200-MR6 in human breast cancer: prognostic significance.
Several in vitro studies stress a potentially important role of interleukin 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 growth 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-MR6 showing that down-regulation or loss of this molecule occurred during the evolution of breast cancer. Gp200-MR6 loss was independent from differentiation, nodal positivity and oestrogen receptor levels as well as patients' age. Loss of the gp200-MR6 molecule was more frequent in lobular cases (P=0.03). The overall survival was better, although not 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 independent of gp200-MR6 status. It is concluded that loss of gp200-MR6 may be one of the mechanisms through which breast cancer cells escape immune surveillance, resulting in an increased metastatic potential and poorer outcome. Evidence of down-regulation of the gp200-MR6 molecule has implications for IL-4-linked toxin therapy and, as IL-4 is an inhibitor of breast epithelial growth, may represent loss of a tumour-suppression mechanism.
Kaklamanis
L
L
Department of Cellular Science, John Radcliffe Hospital, Oxford, UK.
Koukourakis
M I
MI
Leek
R
R
Giatromanolaki
A
A
Ritter
M
M
Whitehouse
R
R
Gatter
K C
KC
Harris
A L
AL
D000704:Analysis of Variance; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000032:analysis* / Q000378:metabolism; D001943:Breast Neoplasms / Q000737:chemistry* / Q000473:pathology / Q000648:ultrastructure*; D066246:ErbB Receptors / Q000032:analysis; D005500:Follow-Up Studies; D006023:Glycoproteins / Q000032:analysis* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D037181:Lectins, C-Type; D008875:Middle Aged; D015778:Minor Histocompatibility Antigens; D009367:Neoplasm Staging; D011379:Prognosis; D011956:Receptors, Cell Surface; D011960:Receptors, Estrogen / Q000032:analysis; D018123:Receptors, Interleukin / Q000378:metabolism; D019948:Receptors, Interleukin-4
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000951:Antigens, Neoplasm; C093569:DEC-205 receptor; D006023:Glycoproteins; D037181:Lectins, C-Type; D015778:Minor Histocompatibility Antigens; D011956:Receptors, Cell Surface; D011960:Receptors, Estrogen; D018123:Receptors, Interleukin; D019948:Receptors, Interleukin-4; D066246:ErbB Receptors