Immunohistochemical study of Ki-67 and DNA topoisomerase II in human endometrium.

Topoisomerase II (topo II) separates the chromosomes at the end of mitosis, and its expression is limited mostly to the S-to-G2/M phases of the normal cell cycle. We examined the expression of topo II immunohistochemically in 56 specimens of the human endometrium that were retrieved from surgical pathology files. Specimens included proliferative phase mucosa (n = 7), secretory phase mucosa (n = 5), nonatypical adenomatous hyperplasia (n = 7), atypical adenomatous hyperplasia (n = 7) and endometrioid adenocarcinoma (n = 30). We calculated the labeling index (LI) for topo II and correlated the findings with the LI for Ki-67. A significant positive correlation was obtained between the Ki-67 and topo II LIs in all of the specimens examined. The levels of the topo II and Ki-67 LIs in secretory phase endometrium were each significantly lower than in the other cases examined. The levels of the topo II and Ki-67 LIs in adenocarcinoma were significantly higher than those in proliferative phase endometrium and nonatypical hyperplasia. There were no significant differences between atypical hyperplasia and adenocarcinoma in the Ki-67 and topo II LIs. The level of the topo II LI in atypical hyperplasia was significantly higher than that in nonatypical hyperplasia, whereas the Ki-67 LI did not differ between atypical and nonatypical hyperplasia. The levels of the Ki-67 LI were significantly higher than those of the topo II LI in proliferative phase endometrium and in nonatypical hyperplasia, but no significant differences were observed between the LIs in atypical hyperplasia and adenocarcinoma. Topo II immunostaining can identify proliferative cells in routinely processed surgical pathology specimens of human endometrium. The relative overexpression of topo II as compared with Ki-67 in adenocarcinoma suggests a dysregulation or qualitative alteration in topo II associated with malignancy, as reported in other tissues. Such over-expression in atypical hyperplasia might reflect the possible premalignant nature of this type of endometrial hyperplasia.