Monoclonal antibody MA454 reveals a heterogeneous expression pattern of MAGE-1 antigen in formalin-fixed paraffin embedded lung tumours

Cancer/testis (CT) antigens such as those encoded by the MAGE-gene family a re expressed in a wide Variety of malignant neoplasms. In normal tissues, e xpression is generally restricted to testis, Current knowledge of the expre ssion pattern of CT antigens is mainly based on mRNA analysis. Little is kn own about actual protein expression. We previously developed MA454, a monoc lonal antibody (mAb) to MAGE-1 recombinant protein. By employing antigen re trieval techniques, we show that MA454 is reactive on formalin-fixed paraff in-embedded tissues. Immunohistochemical (IHC) analysis of a normal tissue panel revealed staining solely in germ cells of estes, A series of 59 lung tumours was co-typed for MAGE-1 expression by RT-PCR and by immunohistochem istry with MA454, MA454 was positive in 19/59 cases (32%). MAGE-1 mRNA was found in 17 of the 54 cases (32%) available for RT-PCR. Of the 19 MA454-rea ctive tumours, 15 showed a highly heterogeneous pattern of expression. The other 4 MA454 positive cases revealed immunoreactivity in >25% of tumour ar eas. Of the 53 cases typed for both, mRNA and protein expression, 48 co-typ ed whereas 5 cases were discrepant, a likely consequence of heterogeneous M AGE-1 expression. The predominantly focal expression of MAGE-1 suggests tha t this antigen might not be sufficient as a sole target for immunotherapeut ic approaches. (C) 2000 Cancer Research Campaign.