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 parathyroid gland is generally believed to be low, but has never previously been measured directly, although, as in other tissues, it is relevant to the pathogenesis of neoplasia.

METHODS

We retrieved embedded tissue blocks of parathyroids removed at autopsy from 39 patients without hypercalcaemia 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-cycle marker, using the MIB-1 antibody with microwave antigen retrieval, and tonsil as positive control. Using an eyepiece graticule with unbiased square-counting frame, positively labelled chief cells were counted in large squares and total chief cells in small squares in fields selected by systematic random sampling from multiple regions. A minimum of 15 x 10(3) chief cells were accumulated in each case. The prevalence of Ki-67 positive cells per 10(4) cells (label index or LI) was converted 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 geometric mean cell-birth rate was 5.24%/year and 95% confidence interval 0.81-33.8%/year. We found no significant effect of age, sex, race, or duration of tissue storage. The distribution of cells conformed to a Poisson distribution, and there was no difference between central and peripheral regions.

CONCLUSIONS

(1) Our results establish the human parathyroid gland as a conditionally renewing tissue with very low basal cell-birth rate; other reports of much higher LI values are probably due to selective and consequently biased sampling. (2) Since the total number of cell divisions is a major determinant of the total number of mutations, our results place some constraints of possible mechanisms for parathyroid neoplasia.