Loss of interleukin 4 receptor-associated molecule gp200-MR6 in human breast cancer: prognostic significance.

Abstract

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.

• Authors: L Kaklamanis, M I Koukourakis, R Leek, A Giatromanolaki, M Ritter, R Whitehouse, K C Gatter, A L Harris
• Journal: British journal of cancer (Br J Cancer) Vol. 74 Issue 10 Pg. 1627-31 (Nov 1996) ISSN: 0007-0920 [Print] England
• PMID: 8932345 (Publication Type: Journal Article)

Chemical References

• Antibodies, Monoclonal
• Antigens, CD
• Antigens, Neoplasm
• DEC-205 receptor
• Glycoproteins
• Lectins, C-Type
• Minor Histocompatibility Antigens
• Receptors, Cell Surface
• Receptors, Estrogen
• Receptors, Interleukin
• Receptors, Interleukin-4
• ErbB Receptors

Topics

• Analysis of Variance
• Antibodies, Monoclonal
• Antigens, CD (metabolism)
• Antigens, Neoplasm (analysis, metabolism)
• Breast Neoplasms (chemistry, pathology, ultrastructure)
• ErbB Receptors (analysis)
• Follow-Up Studies
• Glycoproteins (analysis, metabolism)
• Humans
• Immunohistochemistry
• Lectins, C-Type
• Middle Aged
• Minor Histocompatibility Antigens
• Neoplasm Staging
• Prognosis
• Receptors, Cell Surface
• Receptors, Estrogen (analysis)
• Receptors, Interleukin (metabolism)
• Receptors, Interleukin-4