THE BASAL RATE OF CELL-PROLIFERATION IN NORMAL HUMAN PARATHYROID TISSUE - IMPLICATIONS FOR THE PATHOGENESIS OF HYPERPARATHYROIDISM

BACKGROUND The basal rate of cell proliferation in the human parathyro id gland is generally believed to be low, but has never previously bee n measured directly, although, as in other tissues, it is relevant to the pathogenesis of neoplasia. METHODS We retrieved embedded tissue bl ocks of parathyroids removed at autopsy from 39 patients without hyper calcaemia or abnormal renal function, aged 18 to 76 years (mean 47.6). New sections were cut and examined for expression of Ki-67, a cell-cy cle marker, using the MIB-1 antibody with microwave antigen retrieval, and tonsil as positive control. Using an eyepiece graticule with unbi ased square-counting frame, positively labelled chief cells were count ed in large squares and total chief cells in small squares in fields s elected by systematic random sampling from multiple regions. A minimum of 15x10(3) chief cells were accumulated in each case. The prevalence of Ki-67 positive cells per 10(4) cells (label index or LI) was conve rted to cell birth rate assuming that the duration of Ki-67 expression was 24 hours. In ten cases, the entire section was examined; a map of the distribution of the positive cells was reconstructed, and divided into outer and inner regions. RESULTS The geometric mean value for LI was 1.44/10(4), and multiplicative SD 2.54. The corresponding geometr ic mean cell-birth rate was 5.24%/year and 95% confidence interval 0.8 1-33.8%/year. We found no significant effect of age, sex, race, or dur ation of tissue storage. The distribution of cells conformed to a Pois son distribution, and there was no difference between central and peri pheral regions. CONCLUSIONS (1) Our results establish the human parath yroid gland as a conditionally renewing tissue with very low basal cel l-birth rate; other reports of much higher LI values are probably due to selective and consequently biased sampling. (2) Since the total num ber of cell divisions is a major determinant of the total number of mu tations, our results place some constraints on possible mechanisms for parathyroid neoplasia.