INCREASED BINDING-CAPACITY OF RECEPTORS FOR THE EPIDERMAL GROWTH-FACTOR IN BENIGN THYROID-NODULES AND THYROID MALIGNANCIES

To determine the role of epidermal growth factor (EGF) receptors in th yroid tumorigenesis, EGF binding was compared in membranes from malign ant and from benign thyroid tumors. Surgical specimens were obtained f rom 28 patients with thyroid carcinomas (3 papillary, 13 follicular, 6 undifferentiated, and 6 medullary carcinomas) and from 30 patients wi th benign thyroid tumors (15 scintigraphically functional and 15 nonfu nctional nodules). In 30 cases normal tissue adjacent to the tumor was also obtained. EGF binding was seen to be increased not only in thyro id carcinomas but also in benign thyroid tumors, particularly in funct ional thyroid adenomas. The highest EGF binding was found in undiffere ntiated carcinomas. A direct comparison of the EGF binding characteris tics in tumor and adjacent normal thyroid tissue revealed that the inc reased binding of EGF is due mainly to an increase in the number of bi nding sites rather than an alteration in receptor affinities. EGF bind ing capacities were 18.4 +/- 16.7 fmol/mg protein in thyroid carcinoma s and 10.5 +/- 5.2 fmol/mg in the corresponding normal tissue (P<0.05, K(d) 0.84 +/- 0.26 nM, n = 11). In autonomously functioning thyroid a denomas binding capacities were 14.2 +/- 8.2 fmol/mg in the nodules an d 8.9 +/- 4.8 fmol/mg in normal tissue (P<0.01, K(d) 0.73 +/- 0.62 nM, n = 15). In conclusion, EGF receptor levels are increased not only in malignant thyroid tumors but also in well-differentiated benign thyro id nodules. The data indicate that an increased expression of EGF rece ptors, although likely to be important in the regulation of thyroid gr owth in vivo, is not by itself associated with malignant cell transfor mation and loss of differentiated function.