DNA topoisomerase IIα 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 G0 of the cell cycle. A cell cycle-related intranuclear protein, topoisomerase IIα (topoIIα), 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 topoIIα to evaluate their value in the diagnosis of adrenocortical malignancy. We detected Ki-67 and topoIIα immunohistoreactivity in the nuclei of each case we examined. There was a significant positive correlation (r = 0.927) between the Ki-67 and topoIIa labeling indexes (LIs), the percentage of positive cells. In normal adrenal cortex and adenoma, the LIs for Ki-67 and topoIIα 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 topoIIα 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 topoIIα and Ki-67 LIs of more than 2.5, whereas none of the adenomas did. The topoIIα 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 topoIIα could help to differentiate carcinoma from adenoma in resected adrenocortical neoplasms and might predict aggresive biologic behavior in carcinomas.