REDUCED EXPRESSION OF INTERLEUKIN-6 IN UNDIFFERENTIATED THYROID-CARCINOMA - IN-VITRO AND IN-VIVO STUDIES

Cytokines appear to play an important role in the development and prog ression of epithelial tumors. Cultured normal human thyroid follicular cells constitutively release high levels of interleukin-6 (IL-6) and IL-8, together with low to moderate levels of transforming growth fact or-alpha (TGF-alpha) and TGF-beta, IL-6 appears to play multiple funct ions in thyroid physiology and disease, Because certain data indicate an inverse relationship between IL-6 production and epithelial tumor a ggressiveness, we used both tissue culture methods and histochemical t echniques to search for possible alterations of cytokine expression in thyroid carcinomas. As compared to cultures from normal tissue and we ll-differentiated carcinoma, production of IL-6 was strongly down-regu lated in cultures derived from undifferentiated carcinoma, In contrast , levels of IL-8, TGF-alpha, and TGF-beta produced by neoplastic TFC w ere similar to those produced by normal cells. Actually, production of TGF-or was slightly enhanced in cultures from well-differentiated car cinoma. Immunoassay results were confirmed by reverse transcriptase-PC R analysis, Immunohistochemistry of human thyroid carcinomas (n = 99) and normal thyroid tissue (n = 85) showed that immunoreactive IL-6 was strongly diminished in undifferentiated forms (n = 34) and slightly r educed in well-differentiated carcinoma (n = 65), In agreement with th e in vitro results, TGF-alpha expression was significantly increased i n neoplastic thyrocytes, as compared to their normal counterpart, The results indicate that, as in the mammary and salivary glands, down-reg ulation of IL-6 expression may represent a marker of undifferentiated thyroid carcinoma.