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Pituitary Unit of the Department of Neurosurgery (M.L., P.M., R.B., M.G.), Department of Pathology (F.M., M.R.T.), Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele, University Vita-Salute, 20132 Milan, Italy; and Departments of Internal Medicine (E.C., D.G., F.C.) and Pathology (M.P.), Ospedale Molinette, University of Turin, and Department of Neurosurgery (G.F.), Centro Traumatologico Ortopedico, 10100 Turin, Italy
Address all correspondence and requests for reprints to: Marco Losa, M.D., Department of Neurosurgery, Istituto de Ricovero e Cura a Carattere Scientifico San Raffaele, Via Olgettina 60, 20132 Milan, Italy. E-mail: losa.marco{at}hsr.it
Abstract
To investigate the effects of octreotide administration on the growth rate of GH-secreting pituitary adenomas, we measured both the Ki-67 labeling index (LI) and the apoptotic index in tumor specimens from octreotide-treated or matched untreated acromegalic patients. Thirty-nine patients who received octreotide until the day of or the day before surgery and 39 untreated patients matched for sex, age, tumor size, extension, and invasiveness were studied. Immunocytochemical analysis was performed on paraffin-embedded material using a monoclonal antibody (MIB-1) directed against a proliferation-associated nuclear antigen, Ki-67, to measure the growth fraction. Apoptosis was assessed by the terminal deoxynucleotidyl transferase-mediated deoxy-UTP nick endlabeling method, using a monoclonal antibody recognizing areas of DNA fragmentation. The Ki-67 LI and apoptosis were counted on separate slides in at least 1000 evaluable cells.
Octreotide-treated patients showed a lower Ki-67 LI (1.8 ± 0.3%) than untreated controls (3.8 ± 0.7%; P < 0.02). Overall, the mean Ki-67 LI of treated patients was 53% lower than that in untreated patients. The antiproliferative effect of octreotide occurred independently of tumor extension and invasiveness. Octreotide-treated and untreated patients showed similar apoptotic indexes (0.6 ± 0.2% and 0.8 ± 0.3%, respectively). There was a positive correlation between the Ki-67 LI and the apoptotic index (r = 0.29; P < 0.03).
Our study demonstrates that acromegalic patients receiving chronic octreotide treatment have a lower value of the proliferation marker Ki-67, but no significant difference in the apoptotic index compared with matched untreated patients. The antiproliferative effect of octreotide on GH-secreting adenomas should imply a lower risk of tumor growth during long-term chronic treatment with the drug.
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