Expression of Growth Factors and Growth Factor Receptors in Normal and Tumorous Human Thyroid Tissues

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Abstract
A number of growth factors have been implicated as stimuli of thyroid cell proliferation; overexpression of these growth factors and/or their receptors may play a role in the growth of thyroid tumors. To determine if immunohistochemical detection of growth factors and/or their receptors correlates with morphological alterations in proliferative lesions of thyroid, we examined the localization of epidermal growth factor (EGF), transforming growth factor-α (TGF-α) and their common receptor, EGF-receptor (EGF-R), insulin-like growth factor-1 (IGF-1), IGF-1-receptor (IGF-R) and IGF binding proteins (IGFBP)-l, -2, -3, and -4, nerve growth factor (NGF), and its receptor NGF-receptor (NGF-R), transforming growth factor-β (TGF-β), and basic fibroblast growth factor (bFGF), in normal thyroid tissue and various thyroid tumors. We applied the streptavidin-biotin technique to formalin-fixed, paraffin-embedded tissues. We studied 8-16 different cases of each of the following: normal human thyroid, multinodular hyperplasia, follicular adenoma, papillary carcinoma, follicular carcinoma, medullary carcinoma, and anaplastic carcinoma. EGF, TGF-α, and their receptor EGF-R were widely expressed in normal thyroid and in all the thyroid lesions examined. IGF-1 and IGFBP-1 were diffusely present in all different thyroid tissues as well. There was no difference in staining intensity or distribution that correlated with the pathological process. IGFBP-4 seemed to have a variable expression. IGFBP-2 and -3 were detected only in medullary carcinomas. NGF immunoreactivity was found in thyroid tissues and tumors of all types; interestingly, NGF-R staining was found in the vascular stroma and immunoreactivity correlated with the degree of vascularization, but no staining was seen in normal or lesional thyroid cells. TGF-β expression was highly variable, whereas bFGF was not detected by this method in thyroid tissues. This study indicates that growth factors and growth factor receptors are expressed by thyroid follicular cells and C-cells. While they most likely play a role in cell regulation and proliferation in these tissues, their immunohistochemical profile does not correlate with the pathological condition.

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