title: Bcl-2, p53 and MIB-1 expression in normal and neoplastic parathyroid tissues.
abstract: 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.
authors.affiliation: Dipartimento di Oncologia, Università di Pisa, Italy.
authors.forename: A G
authors.initials: AG
authors.lastname: Naccarato
authors.forename: C
authors.initials: C
authors.lastname: Marcocci
authors.forename: P
authors.initials: P
authors.lastname: Miccoli
authors.forename: A G
authors.initials: AG
authors.lastname: Bonadio
authors.forename: L
authors.initials: L
authors.lastname: Cianferotti
authors.forename: E
authors.initials: E
authors.lastname: Vignali
authors.forename: G
authors.initials: G
authors.lastname: Cipollini
authors.forename: P
authors.initials: P
authors.lastname: Viacava
mesh_terms: D000236:Adenoma / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000096:biosynthesis*; D010280:Parathyroid Glands / Q000378:metabolism* / Q000473:pathology; D010282:Parathyroid Neoplasms / Q000378:metabolism* / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*
chemical_list: D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; D019394:Ki-67 Antigen; D009687:Nuclear Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53