Topoisomerase IIα Expression in Pituitary Adenomas and Carcinomas: Relationship to Tumor Behavior

Abstract

DNA topoisomerase IIα (Topo IIα) is a molecular and immunohistochemical marker that indicates proliferation rate and is the target for several antineoplastic agents. The present immunohistochemical study of a large series of surgically removed pituitary tumors was designed to assess the prognostic significance of Topo IIα expression relative to patient age, gender, tumor type and size, invasiveness, metastasis, MIB-1–labeling index and angiogenesis. Changes of Topo IIα expression in the tumors treated with bromocriptine and octreotide, a long-acting somatostatin analogue were also investigated. Topo IIα immunopositivity was detected only in the nuclei of tumor cells. Gonadotroph adenomas, null cell adenomas, and ACTH-producing adenomas had the lowest Topo IIα indices, whereas primary pituitary carcinomas and silent type 3 adenomas presented the highest counts. The statistical study demonstrated no significant correlation between Topo IIα expression, patient gender, and vascularity. In contrast, significant negative correlation was found between Topo IIα expression and patient age. Topo IIα expression was significantly higher in invasive than noninvasive tumors. A tendency to have higher counts was also observed in microadenomas compared with in macroadenomas. Although Topo IIα and MIB-1 indices were similar in most tumor types, no significant correlation between Topo IIα and MIB-1–labeling indices (r = .16, P = .09) was found. Only non-functioning adenomas showed positive correlation (r = .41, P = .006) between both proliferation markers. Our results demonstrated a significant decrease in Topo IIα index in octreotide-treated, GH-producing adenomas, compared with untreated tumors, but no significant changes were observed in bromocriptine-treated, PRL-producing adenomas. The present study showed no significant advantage of Topo IIα over MIB-1 as a prognostic marker; however, Topo IIα may provide crucial information regarding selection of adenohypophyseal tumors responsive to antineoplastic therapy, such as invasive pituitary adenomas and pituitary carcinomas, which exhibit a high Topo IIα index.