CELL-PROLIFERATION AND APOPTOSIS IN NORMAL AND PATHOLOGICAL HUMAN ADRENAL

Cell proliferation and programmed cell death play important roles in t he maintenance of tissue dynamics. The adrenal cortex has been known a s a cell renewal tissue, We studied cell proliferation by Ki67 immunos taining and programmed cell death or apoptosis by a recently developed 3'-OH nick end labeling technique. Fifteen cases of normal human adre nal; 22 cases of adrenocortical adenoma including Cushing's adenoma (f ive cases), aldosteronoma (nine cases), and nonfunctioning adenoma (ei ght cases); and six cases of adrenocortical carcinoma were examined. I n normal adrenal cortex, Ki67 immunoreactivity was predominantly obser ved in the zona fasciculata in all the cases examined, whereas cortica l cells positive for nick end labeling were present in the zona reticu laris in all cases and in the zona glomerulosa in five cases. These re sults suggest that the ''cell migration'' or ''centripetal'' theory is also applicable in cell turnover of normal human adrenal cortex, and cortical cells may move in two directions, from fasciculata to reticul aris and from fasciculata to glomerulosa in some instances. CD68-posit ive sinusoidal lining cells, which are considered to ingest the cells undergoing apoptosis, were present throughout the cortex. In adrenocor tical adenoma, Ki67 immunoreactivity was observed in all cases, and tu mor cells positive for nick end labeling were observed in 12 cases (Cu shing's adenoma in three cases, aldosteronoma in four cases, and nonfu nctioning adenoma in five cases). In adrenocortical carcinoma, Ki67 im munoreactivity was observed in all the cases, and its labeling index w as significantly higher than that of normal adrenal and adrenocortical adenoma. Carcinoma cells positive for nick end labeling were observed in four cases, and there were no significant differences of nick end labeling index among normal adrenal, adenoma, and carcinoma. No specif ic patterns were observed in intratumoral distribution of nick end lab eling or cell proliferation examined by Ki67 immunostaining in adrenoc ortical neoplasms. In the human adrenal gland, apoptosis appears to pl ay important roles in the maintenance of organized cortical cell turno ver in normal cortex and in tumor cell dynamics in adrenocortical aden omas.