Immunohistochemical identification of receptors for epidermal growth factor in tumor endothelium may be affected by cross-reactivity to blood group A antigen.

It has been reported that endothelium in malignant glioma stains with a commercial antibody raised against the receptor for epidermal growth factor (EGFr) on A431 cells (clone 29.1). In this report, this antibody was used to study the immunohistochemical expression of EGFr in benign and malignant ovarian, mid-gut carcinoid, and thyroid neoplasms using the avidin-biotin-peroxidase complex technique. Eighteen of the 37 ovarian neoplasms, 4 of the 10 thyroid neoplasms, and 14 of 28 mid-gut carcinoid tumors expressed strong and distinct endothelial staining, whereas staining results of the remaining tumors were negative. The endothelial nature of the staining was verified by staining serial sections with Ulex europaeus agglutinin-I. The staining was independent of that obtained with an antibody raised against a synthetic peptide consisting of residues 985 to 996 from the cytoplasmic domain of EGFr (clone F4). All positive staining occurred in patients determined to be of blood groups A or AB, whereas samples from patients with blood groups B or O were negative. Immunoabsorption of the antibody with centrifuged erythrocytes from a blood group A donor, but not from a blood group B donor, abolished the positive staining. The data indicate that positive staining of tumor endothelium with this antibody is due to cross-reactivity with blood group A antigen. The results obtained challenge the validity of previously performed immunohistochemical studies in which monoclonal antibodies raised against the EGFr of A431 cells have been used, and in which the epitope for the monoclonal antibody has not been determined.