FIBROBLAST-GROWTH-FACTOR-1 AND FIBROBLAST-GROWTH-FACTOR-2 AND FIBROBLAST-GROWTH-FACTOR-RECEPTOR-1 ARE ELEVATED IN THYROID HYPERPLASIA

We have previously reported increased expression of fibroblast growth factor (FGF-1 and FGF-2) in benign and malignant human thyroid neoplas ia. To determine the role of these factors in thyroid hyperplasia we h ave examined their expression in multinodular goiter and compared find ings 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 pe rformed on sections from multinodular goiters (n = 18) and normal thyr oid (n = 7). Cytoplasmic staining for FGF-1, FGF-2, and FGFR-1 was sco red on a scale of 0 (no staining) to 3 (heavy staining) and expressed as a percentage of total cells stained. Confocal microscopy of immunof luorescent staining for FCF-1, FGF-2, and FGFR-1 in sections of multin odular goiter (n = 3) and normal thyroid (n = 3) provided quantitation of immunostaining. FGF-1 expression was significantly increased in mu ltinodular goiter thyroid expressed FGF-1 (P < 0.0001). When expressio n of FGF-2 was examined, 77% of the follicular cells in multinodular g oiter compared with 5% in normal thyroids were immunopositive (P < 0.0 001). Confocal microscopy revealed that the intensity was 160 times gr eater in follicular cells in sections of multinodular goiters when com pared with normal. When expression of FGFR-1 was analyzed, 89% of the follicular cells in multinodular goiter stained positively, compared w ith 15% of follicular cells in sections of normal thyroid. Confocal mi croscopy revealed a 6-fold increase in intensity of FGFR-1 expression in follicular cells of multinodular goiter (P < 0.05). In addition, th ere was significant nuclear expression of FGFR-1 in multinodular goite r contrasting with negligible expression in normal thyroid. These data show that enhanced expression of FGF-1, FGF-2, and FGFR-1 accompany t hyroid hyperplasia and are not exclusively associated with the neoplas tic state. These factors may be involved in the pathogenesis of uncont rolled thyroid growth observed in these conditions.