Immunohistochemistry of pure growth hormone-containing and mixed growth hormone/prolactin-containing pituitary adenomas
Evgeniya Marova, Petr Yushkov, Natalja Molitvoslovova & Elena Luljeva
Transsphenoidal surgery is the most efficient primary treatment for acromegaly. However, some patients do not meet remission criteria after operation. Mixed growth hormone (GH)/prolactin (PRL)-secreting pituitary adenomas are known to predict poor surgical outcome. The aim of our study was to evaluate immunohistochemical markers in pure GH-and mixed GH/PRL-containing tumors and to investigate their prognostic value. In our study we included 39 acromegalic patients, who underwent transsphenoidal surgery as primary treatment. We used immunohistochemical staining of removed adenomas for PRL to evaluate hormonal content of adenomas cells; for proliferation marker (Ki-67), angiogenesis index (CD31) and marker for malignancy potential (galectin-3) to assess the biological tumor behavior. In addition to immunostaining of removed pituitary adenomas we evaluated clinical, hormonal and radiological data based on magnetic resonance imaging (MRI). Immunohistochemistry showed mixed GH/PRL-containing adenomas in 9 patients (23%), whereas pure GH-secreting adenomas in 30 cases (77%). Ki-67 was present in all mixed adenomas, but not in pure GH-secreting tumors. Galectin-3 was positive in 2 GH/PRL-cosecreting tumors (22%) and 9 pure GH adenomas (30%). CD31 was found in 3 mixed tumors (33%) and 13 pure GH adenomas (43%). In patients with GH/PRL co-secreting tumors MRI-predictors of unsuccessful surgical outcome were present: large size (P=0.0007, under Mann-Whitneys test) and intracavernous extension of adenomas (P=0.0262, under two-tailed Fishers exact test). In addition, there were no cases of remission in patients with mixed GH/PRL-containing tumors. In conclusion, evaluation of immunohistochemical predictors of removed adenomas in combination with immunostaining for PRL in acromegalic patients gives the additional information which can determine surgical outcome and postoperative adjunctive therapy for such patients.