Nodular foci in parathyroid adenomas and hyperplasias: an immunohistochemical analysis of proliferative activity.

Samples of normal, hyperplastic, and neoplastic parathyroid tissues were analyzed for proliferative activity to determine (1) whether a higher number of proliferating cells were detectable in adenoma and hyperplasia versus normal tissues; (2) whether there was a difference in the number of proliferating cells in adenoma versus hyperplasia; and (3) whether there was a relationship between nodularity and proliferative rate in both adenoma and hyperplasia. Formalin-fixed, paraffin-embedded tissue from 21 patients with parathyroid adenoma and 10 patients with hyperplasia (two primary, six secondary, and two tertiary) was analyzed by immunohistochemistry with the monoclonal antibody PC10 to proliferating cell nuclear antigen (PCNA) and, in a subset of cases, with Ki-67 (MIB 1) as markers of cell proliferation. The results were that (1) no proliferating cells were found in normal glands or residual rim of "suppressed" parathyroid tissue; (2) the most intense proliferative activity was confined to nodular areas in both adenomas (57% nodular) and hyperplasias (80% nodular); (3) when fields of highest number of labeled nuclei were chosen, PCNA counts were higher in adenomas than in hyperplasia in both nodular and diffuse areas (P < .05); and (4) the number of nuclei immunoreactive for Ki-67 (MIB-1) was consistently and proportionally lower (range, 13% to 45%; mean, 32%) than the number of those immunoreactive for PCNA, although the nodular pattern was maintained. These findings demonstrate that nodules within parathyroid adenomas and hyperplasias contain subpopulations of cells with a consistently higher proliferative rate than nonnodular areas. Cells within these nodules may be more likely to develop genetic abnormalities that have been observed in hyperplastic and neoplastic parathyroid tissues.