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Fibroblast Growth Factors 1 and 2 and Fibroblast Growth Factor Receptor 1 Are Elevated in Thyroid Hyperplasia

Departments of ENT Surgery (S.D.T., J.C.W.) and Medicine (J.A.F., J.M.V., M.C.S., M.C.E.), University of Birmingham, Queen Elizabeth Hospital, Edgbaston, Birmingham B15 2TH, United Kingdom

Abstract

We have previously reported increased expression of fibroblast growth factor (FGF-1 and FGF-2) in benign and malignant human thyroid neoplasia. To determine the role of these factors in thyroid hyperplasia we have examined their expression in multinodular goiter and compared findings with those in normal thyroid tissue. Because the effects of FGF-1 and FGF-2 are predominantly mediated through the FGF receptor-1 (FGFR-1), its expression has also been examined. Immunocytochemistry was performed on sections from multinodular goiters (n = 18) and normal thyroid (n = 7). Cytoplasmic staining for FGF-1, FGF-2, and FGFR-1 was scored on a scale of 0 (no staining) to 3 (heavy staining) and expressed as a percentage of total cells stained. Confocal microscopy of immunofluorescent staining for FGF-1, FGF-2, and FGFR-1 in sections of multinodular goiter (n = 3) and normal thyroid (n = 3) provided quantitation of immunostaining. FGF-1 expression was significantly increased in multinodular goiter when compared with normal. A mean of 74% of follicular cells in multinodular goiter compared with 9% of follicular cells in normal thyroid expressed FGF-1 (P < 0.0001). When expression of FGF-2 was examined, 77% of the follicular cells in multinodular goiter compared with 5% in normal thyroids were immunopositive (P < 0.0001). Confocal microscopy revealed that the intensity was 160 times greater in follicular cells in sections of multinodular goiters when compared with normal. When expression of FGFR-1 was analyzed, 89% of the follicular cells in multinodular goiter stained positively, compared with 15% of follicular cells in sections of normal thyroid. Confocal microscopy revealed a 6-fold increase in intensity of FGFR-1 expression in follicular cells of multinodular goiter (P < 0.05). In addition, there was significant nuclear expression of FGFR-1 in multinodular goiter contrasting with negligible expression in normal thyroid. These data show that enhanced expression of FGF-1, FGF-2, and FGFR-1 accompany thyroid hyperplasia and are not exclusively associated with the neoplastic state. These factors may be involved in the pathogenesis of uncontrolled thyroid growth observed in these conditions.

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