title: DNA topoisomerase II alpha and Ki-67 in human adrenocortical neoplasms: a possible marker of differentiation between adenomas and carcinomas.
abstract: 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 II alpha (topoII alpha), 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 alpha to evaluate their value in the diagnosis of adrenocortical malignancy. We detected Ki-67 and topoII alpha immunohistoreactivity 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 +/0 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.
authors.affiliation: Department of Pathology, Tohoku University School of Medicine, Sendai, Japan. k-iino@patholo2.med.tohoku.ac.jp
authors.forename: K
authors.initials: K
authors.lastname: Iino
authors.forename: H
authors.initials: H
authors.lastname: Sasano
authors.forename: N
authors.initials: N
authors.lastname: Yabuki
authors.forename: Y
authors.initials: Y
authors.lastname: Oki
authors.forename: A
authors.initials: A
authors.lastname: Kikuchi
authors.forename: T
authors.initials: T
authors.lastname: Yoshimi
authors.forename: H
authors.initials: H
authors.lastname: Nagura
mesh_terms: D000236:Adenoma / Q000737:chemistry* / Q000401:mortality; D000306:Adrenal Cortex Neoplasms / Q000737:chemistry* / Q000401:mortality; D000308:Adrenocortical Hyperfunction / Q000378:metabolism; D000328:Adult; D000367:Age Factors; D000368:Aged; D000951:Antigens, Neoplasm / Q000032:analysis / Q000276:immunology; D014408:Biomarkers, Tumor / Q000032:analysis; D002277:Carcinoma / Q000737:chemistry* / Q000401:mortality; D002455:Cell Division; D002675:Child, Preschool; D004250:DNA Topoisomerases, Type II / Q000032:analysis* / Q000276:immunology; D004268:DNA-Binding Proteins; D005069:Evaluation Studies as Topic; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000032:analysis* / Q000276:immunology; D019394:Ki-67 Antigen / Q000032:analysis* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000473:pathology; D015996:Survival Rate
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D007527:Isoenzymes; D019394:Ki-67 Antigen; D004250:DNA Topoisomerases, Type II