DNA topoisomerase II alpha and Ki-67 in human adrenocortical neoplasms: A possible marker of differentiation between adenomas and carcinomas

Cell kinetic information is valuable in evaluating the diagnosis and/or biologic behavior of various human neoplasms. Monoclonal antibody Ki-67 recognizes the cells other than GO of the cell cycle. A cell cycle-related intranuclear protein, topoisomerase II alpha (topoII<alphla>), separates chromosomes at the end of mitosis. Its expression is mostly limited to the S to G2/M phases of the cell cycle, We studied cell proliferative activity in adrenocortical adenomas (n = 28), carcinomas (n = 17), and normal adrenal glands (n = 6) by immunohistochemical analysis of Ki-67 and topoII to evaluate their value in the diagnosis of adrenocortical malignancy. We detected Ki-67 and topoII alpha in the nuclei of each case we examined. There was a significant positive correlation (r = 0.927) between the Ki-67 and topoII alpha labeling indexes (LIs), the percentage of positive cells. In normal adrenal cortex and adenoma, the LIs for Ki-67 and topoII alpha were 0.48 +/- 0.16 and 0.44 +/- 0.15 for normal and 0.64 +/- 0.11 and 0.72 +/- 0.12 for adenoma, respectively, with no significant differences in the LIs of adenomas and normal adrenals, The Ki-67 and topoII alpha LIs in the carcinomas were 5.84 +/- 1.33 and 6.13 +/- 1.65, respectively; these LIs were significantly higher than the LIs of adenomas, Eleven of 17 carcinomas demonstrated topoII alpha and Ki-67 LIs of more than 2.5, whereas none of the adenomas did. The topoII alpha and Ki-67 LIs in carcinomas with metastasis (11.21 +/- 3.15 and 9.75 +/- 2.31 respectively; n = 7) were significantly higher than in those without metastasis (2.58 +/- 0.61 and 3.12 +/- 0.90, respectively; n = 10). This indicates that immunohistochemical analysis of Ki-67 and topoII alpha could help to differentiate carcinoma from adenoma in resected adrenocortical neoplasms and might predict aggressive biologic behavior in carcinomas.