Proliferative activity in C-cell hyperplasia and medullary thyroid carcinoma. Evaluation by PCNA immunohistochemistry and AgNORs staining.

C cell hyperplasia (CCH) is a preneoplastic lesion that precedes the development of medullary thyroid carcinoma (MTC) in familial cases. It has been hypothesized that CCH progressively acquires the neoplastic phenotype after presenting some genetic changes that involve oncogenes and tumor suppressor genes. The proliferative activity of nodular C cell hyperplasia (NCCH) and early MTC has been assessed by PCNA (Proliferating Cell Nuclear Antigen) immunohistochemistry and nucleolar organizer regions silver staining (AgNOR) in surgical specimens of seven patients with familial MTC. The ratios of PCNA-positive nuclei in NCCH (mean 1.2, range 0.2-4) were lower than in MTC (mean 2, range 1-7%). The AgNOR scores for NCCH (mean 1.53, range 1.10-1.90) were also lower than for MTC (mean 2.10, range 1.90-2.64). The results suggest that C cells progressively acquire a higher proliferative activity in agreement with the severity of the morphologic changes in the process of hyperplasia-neoplasia that leads to widely invasive MTC.