Immunohistochemical study of DNA topoisomerase II in human gastric disorders

Noritaka Yabuki, Hironobu Sasano, Katsuaki Kato, Shuichi Ohara, Takayosi Toyota, Hiroshi Nagura, Mitsuko Miyaike, Naohito Nozaki, Akihiko Kikuchi

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Abstract

Topoisomerase II (topo II) separates chromosomes at the end of mitosis and is also the target for various chemotherapeutic agents. Expression of this enzyme has been demonstrated to increase rapidly at the end of the S to G2/M phase and decrease after the completion of mitosis. We immunolocalized topo II in specimens of both normal and neoplastic human gastric mucosas to evaluate expression of this enzyme. Three different antibodies were used for the immunostaining of topo II (anti-topo IIα isoform, anti-topo IIβ isoform and anti-topo IIα and -β isoforms). There were no significant differences in topo II labeling index (LI) between frozen and paraffin-embedded tissue sections obtained from the same cases. Topo II LI was significantly correlated with Ki67 LI in all of the specimens examined. The area of cells positive for Topo II was much narrower than that of Ki67 in the normal gastric glands, and the pattern of Topo II immunolocalization in both adenomas and adenocarcinomas was also essentially the same as that of Ki67. The topo II LI values (positive cells/1000 cells) for normal gastric gland, adenarea, intestinal-type adenocarcinoma, and diffuse-type adenocarcinoma were 114.7 ± 2.2, 266.7 ± 18.8, 277.6 ± 19.2, and 324.5 ± 5.3, respectively. Significant differences in topo II LI and topo II/Ki67 index were observed between normal and neoplastic mucosas (P < 0.0001) and between adenomas or intestinal-type adenocarcinoma and diffuse-type adenocarcinoma (P < 0.001 and P < 0.01, respectively). Simultaneous measurement of topo IIα and nuclear DNA content by two-parameter flow cytometry revealed that the Jurkat cell line established from acute lymphocytic leukemia cells expressed the enzyme in cells at other than S and G2/M phases of the cell cycle whereas topo-IIα-positive cells were predominantly observed in S and G2/M phases of the cell cycle in the cells from normal lymph nodes. These findings suggest that dysregulation or qualitative changes of topo IIα expression are associated with malignancy. Topo II immunostaining can thus detect proliferating cells in routinely processed tissue sections and can indicate the altered topo IIα expression in human cancers, which may be related to the sensitivity to topo-II-targeted chemotherapeutic agents.

Original languageEnglish
Pages (from-to)997-1007
Number of pages11
JournalAmerican Journal of Pathology
Volume149
Issue number3
Publication statusPublished - 1996 Sep

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Yabuki, N., Sasano, H., Kato, K., Ohara, S., Toyota, T., Nagura, H., Miyaike, M., Nozaki, N., & Kikuchi, A. (1996). Immunohistochemical study of DNA topoisomerase II in human gastric disorders. American Journal of Pathology, 149(3), 997-1007.