Effects of octreotide treatment on the proliferation and apoptotic index of GH-secreting pituitary adenomas

To investigate the effects of octreotide administration on the growth rate of GH-secreting pituitary adenomas, we measured both the Ki-67 labeling ind ex (LI) and the apoptotic index in tumor specimens from octreotide-treated or matched untreated acromegalic patients. Thirty-nine patients who receive d octreotide until the day of or the day before surgery and 39 untreated pa tients matched for sex, age, tumor size, extension, and invasiveness were s tudied. Immunocytochemical analysis was performed on paraffin-embedded mate rial using a monoclonal antibody (MIB-1) directed against a proliferation-a ssociated nuclear antigen, Ki-67, to measure the growth fraction. Apoptosis was assessed by the terminal deoxynucleotidyl transferase-mediated deoxy-U TP nick end-labeling method, using a monoclonal antibody recognizing areas of DNA fragmentation. The Ki-67 LI and apoptosis were counted on separate s lides in at least 1000 evaluable cells. Octreotide-treated patients showed a lower Ki-67 LI (1.8 +/- 0.3%) than unt reated controls (3.8 +/- 0.7%; P < 0.02). Overall, the mean Ki-67 LI of tre ated patients was 53% lower than that in untreated patients. The antiprolif erative effect of octreotide occurred independently of tumor extension and invasiveness. Octreotide-treated and untreated patients showed similar apop totic indexes (0.6 +/- 0.2% and 0.8 +/- 0.3%, respectively). There was a po sitive correlation between the Ki-67 LI and the apoptotic index (r = 0.29; P < 0.03). Our study demonstrates that acromegalic patients receiving chronic octreoti de treatment have a lower value of the proliferation marker Ki-67, but no s ignificant difference in the apoptotic index compared with matched untreate d patients. The antiproliferative effect of octreotide on GH-secreting aden omas should imply a lower risk of tumor growth during long-term chronic tre atment with the drug.