1. ¹Department of Anatomy, Laboratory of Histology, University of Santiago de Compostela Lugo, Spain
2. ²Department of Laboratory Medicine and Pathology, St. Michael's Hospital, University of Toronto, Toronto, Canada
3. ³First Department of Neurosurgery, Toho University, School of Medicine, Tokyo, Japan
4. ⁴Department of Pathology and Laboratory Medicine, Mayo Clinic, Rochester, Minnesota

Correspondence: Bernd W. Scheithauer, M.D., Department of Pathology and Laboratory Medicine, Mayo Clinic, 200 First Street, SW, Rochester, MN 55905. e-mail: scheithauer.bernd@mayo.edu; fax: 507-284-1599

Accepted 7 August 2002.

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 bromocriptine-treated, 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.