Bcl-2, p53 and MIB-1 expression in normal and neoplastic parathyroid tissues.

An altered control of the mechanisms involved in cell proliferation and programmed cell death (apoptosis) might play an important role in parathyroid tumorigenesis. We evaluated by immunohistochemistry the expression of bcl-2 and p53 proteins, as markers of apoptosis control, and MIB-1, as marker of cell proliferation, in a series of normal and neoplastic parathyroid tissues. The specimens were 33 normal parathyroids, 43 parathyroid adenomas and 3 parathyroid carcinomas. Results were scored as positive when more than 1\% of cells were stained for MIB-1 and p53, and more than 10\% for bcl-2. All normal parathyroids showed numerous bcl-2 positive cells (> or = 80\%), low proliferation rate (MIB-1) and no p53 protein expression. Twenty-four (55\%) adenomas were bcl-2 positive; in 16 of these the number of positive cells was high (> 50\%) and immunoreactivity was diffusely distributed within the adenoma; 8 cases showed a zonal staining pattern, in which groups of stained cells were surrounded by negative cells. Nineteen adenomas (45\%) and all carcinomas were bcl-2 negative. A high proliferative rate (MIB-1) was found in all carcinomas and 4 adenomas (9\%); all MIB-1 positive adenomas were bcl-2 negative. p53 was negative in all specimens. No significant differences in serum calcium and intact PTH levels nor in tumor size were found between bcl-2 negative and bcl-2-positive and MIB-1-positive and MIB-1-negative adenomas. An inverse, but not statistically significant (p = 0.06) correlation was observed between the percentage of bcl-2 positive cells and serum calcium level in parathyroid adenomas. In conclusion, parathyroid adenomas are a heterogeneous group of lesions in which the pattern of bcl-2 and MIB-1 protein expression ranges between that of normal parathyroid (bcl-2 positivity and MIB-1 negativity) and that of parathyroid carcinoma (bcl-2 negativity and MIB-1 positivity). The question of whether the finding of the MIB-1 positive-bcl-2 negative phenotype identifies a subgroup of clinically more aggressive adenomas remains to be established.