ANTIPROLIFERATIVE EFFECT OF THE SOMATOSTATIN ANALOG OCTREOTIDE ON GROWTH HORMONE-PRODUCING PITUITARY-TUMORS - RESULTS OF A MULTICENTER RANDOMIZED TRIAL

Objective: To determine and quantify the in vivo effects of octreotide on the cell cycle kinetics of growth hormone-producing pituitary aden omas. Design: A multicenter randomized trial had been conducted to ass ess the clinical efficacy of octreotide, and we studied tissue specime ns from pituitary macroadenomas in 32 patients with acromegaly from th at trial-16 of whom had received 4 months of octreotide therapy before surgical resection and 16 of whom had undergone surgical resection on ly. Material and Methods: All tumors had been fully characterized on t he basis of their immunophenotypic profile and their ultrastructural m orphologic features, Included were 16 densely and 16 sparsely granulat ed somatotroph adenomas, In each case, immunostaining for the cell cyc le-specific nuclear antigen Ki-67 was performed with use of the MIB-1 antibody, The staining reaction was manually quantified, and a tumor g rowth fraction was derived in each case. Results: The mean growth frac tion of tumors exposed to octreotide was suppressed by 83% in comparis on with untreated surgical controls (0.011 +/- 0.004% versus 0.065 +/- 0.016%, respectively; P = 0.0068). The association between octreotide treatment and lower tumor growth fractions was statistically independ ent of tumor subtype, being evident among both sparsely and densely gr anulated somatotroph adenomas. Conclusion: Octreotide exerts a signifi cant antineoplastic effect on somatotroph adenomas, one readily reflec ted at the level of the cell cycle, This antiproliferative response pr ovides insight into several clinicopathologic issues surrounding octre otide therapy for these neoplasms.