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

Abstract

DNA topoisomerase II␣ (Topo II␣) 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 II␣ expression relative to patient age, gender, tumor type and size, invasiveness, metastasis, MIB-1-labeling index and angiogenesis. Changes of Topo II␣ expression in the tumors treated with bromocriptine and octreotide, a long-acting somatostatin analogue were also investigated. Topo II␣ immunopositivity was detected only in the nuclei of tumor cells. Gonadotroph adenomas, null cell adenomas, and ACTH-producing adenomas had the lowest Topo II␣ indices, whereas primary pituitary carcinomas and silent type 3 adenomas presented the highest counts. The statistical study demonstrated no significant correlation between Topo II␣ expression, patient gender, and vascularity. In contrast, significant negative correlation was found between Topo II␣ expression and patient age. Topo II␣ 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 II␣ and MIB-1 indices were similar in most tumor types, no significant correlation between Topo II␣ 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 II␣ index in octreotide-treated, GH-producing adenomas, compared with untreated tumors, but no significant changes were observed in bromocriptinetreated, PRL-producing adenomas. The present study showed no significant advantage of Topo II␣ over MIB-1 as a prognostic marker; however, Topo II␣ 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 II␣ index.

Cyclooxygenase‐2 expression in human pituitary tumors

“…22,23 Because the histologic appearance of pituitary tumors is a poor predictor of aggressive behavior, 24 a number of studies have assessed cell proliferation and angiogenesis markers as predictors of tumor prognosis. [25][26][27][28][29] To obtain deeper insight into the role of COX-2 in pituitary tumor pathobiology, we analyzed the correlation between COX-2 expression and immunolabeling for MIB-1, a cell proliferation marker, as well as microvessel density (MVD), microvessel surface density (MSD), and expression of hypoxia-inducible factor-1␣ (HIF-1␣).…”

Topoisomerase 2 alpha as a prognostic factor in pituitary tumors

“…In order to treat patients more effectively, rather than to await confirmation of tumor recurrence by MR imaging, suitable markers of invasiveness and proliferation of pituitary adenomas are sought to select patients with atypical pituitary adenomas. In our group of 60 patients, 73% expressed Topo2A, against 76%, reported by Vidal et al [16].…”

“…Wolfsberger et al [17] found no dependence of Topo2A expression on tumor size, while Vidal et al [16] suggested a negative correlation.…”

“…However, Wolfsberger et al [17] found that female gender is significantly associated with higher Topo2A index. Vidal et al [16] found a negative correlation between Topo2A expression and patient age.…”

“…Determination of Topo2A activity enabled the group of invasive pituitary adenomas to be distinguished [15,16]. In pituitary adenomas, Wolfsberg et al [17] found a strong correlation between MIB-1 and Topo2A expression.…”