Immunocytochemically detectable TGF-beta associated with malignancy in thyroid epithelial neoplasia

The possible role of changes in TGF-beta expression in the multistage development of thyroid cancer was assessed. The presence of TGF-beta 1 in thyroid epithelial cells was analyzed in sections of normal and tumor tissue using an immunoperoxidase technique employing an antibody directed against the amino-terminal 30 amino acids of mature TGF-beta 1. Specific immunostaining was clearly detected in epithelial cells in 58% of malignant thyroid tumours (including follicular, papillary, and anaplastic variants). However, no positive cells were seen in any of 7 benign tumors nor in any normal thyroid epithelium. Within the cancer group as a whole, there was no significant correlation with pathological grade or clinical stage of tumor but in one subgroup--follicular carcinomas--a significant association was noted between TGF-beta immunostaining and the presence of a specific mutation of the H-ras oncogene (codon 61, gln----arg). We conclude that a major alteration in expression of TGF-beta occurs specifically in the malignant stage of tumor development in thyroid follicular epithelium and speculate on its possible role in this process.