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In pituitary tumors markers of proliferation and progression essential for treatment and follow-up are searched Objectives: We studied topoisomerase 2 alpha (Topo2A) expression in different types of pituitary adenomas in order to evaluate its prognostic potential in patients with hypophyseal tumors. Patients and methods: In a retrospective study of 60 patients of mean age 46.7±17.6 years who underwent pituitary tumor surgery, expression of Topo2A, by immunohistochemistry, was analysed quantitatively with respect to histopathology, tumor features, clinical symptoms, MR imaging and post-operative recurrence/progression of disease. Results: Topo2A was expressed in 73% of (44/60) pituitary adenoma. The highest Topo2A indices were observed in ACTH-secreting pituitary tumors (median:1.13% [0.37-1.21]), followed by silent-ACTH tumors (0.94%[0.89-1.0]), and hormone immunonegative adenomas (0.8%[0.65-1.55]). No differences in expression with respect to patient age or gender were observed. Statistically significant relations were found between Topo2A index and tumor size, its invasiveness, pathological ocular tests and recurrence of tumor growth in postoperative observation. In patients with Topo2A index >1% the relative risk of tumor recurrence is higher by a factor of 3.5 (95%CI:1.8-6.9), P<0.001. After pre-treatment acromegaly patients with somatostatin analogues decrease in median Topo2A expression was observed, compared with untreated patients (0.0% [0.0-0.22] vs 0.71%[0.17-1.0], P<0.05). Conclusions: In our study group, Topo2A index exceeding 1% was found to be a prognostic factor for recurrence/progression of tumors, especially in patients with hormonally inactive adenomas, to be selected for intensive postoperative treatment. In acromegaly, application of somatostatin analogues inhibits Topo2A expression, providing molecular evidence of the effectiveness of these analogues.

Topoisomerase 2 alpha as a prognostic factor in pituitary tumors