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

Marco Losa, Enrica Ciccarelli, Pietro Mortini, Raffaella Barzaghi, Daniela Gaia, Giuliano Faccani, Mauro Papotti, Francesca Mangili, Maria Rosa Terreni, Franco Camanni, Massimo Giovanelli

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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 end-labeling 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.

Original languageEnglish
Pages (from-to)5194-5200
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Volume86
Issue number11
DOIs
Publication statusPublished - 2001

Fingerprint

Growth Hormone-Secreting Pituitary Adenoma
Octreotide
Labeling
Tumors
Therapeutics
Neoplasms
Apoptosis
Growth
Nuclear Antigens
DNA Nucleotidylexotransferase
DNA Fragmentation
Paraffin
Surgery
Ambulatory Surgical Procedures
Adenoma
Monoclonal Antibodies

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Effects of octreotide treatment on the proliferation and apoptotic index of GH-secreting pituitary adenomas. / Losa, Marco; Ciccarelli, Enrica; Mortini, Pietro; Barzaghi, Raffaella; Gaia, Daniela; Faccani, Giuliano; Papotti, Mauro; Mangili, Francesca; Terreni, Maria Rosa; Camanni, Franco; Giovanelli, Massimo.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 86, No. 11, 2001, p. 5194-5200.

Research output: Contribution to journalArticle

Losa, M, Ciccarelli, E, Mortini, P, Barzaghi, R, Gaia, D, Faccani, G, Papotti, M, Mangili, F, Terreni, MR, Camanni, F & Giovanelli, M 2001, 'Effects of octreotide treatment on the proliferation and apoptotic index of GH-secreting pituitary adenomas', Journal of Clinical Endocrinology and Metabolism, vol. 86, no. 11, pp. 5194-5200. https://doi.org/10.1210/jc.86.11.5194
Losa, Marco ; Ciccarelli, Enrica ; Mortini, Pietro ; Barzaghi, Raffaella ; Gaia, Daniela ; Faccani, Giuliano ; Papotti, Mauro ; Mangili, Francesca ; Terreni, Maria Rosa ; Camanni, Franco ; Giovanelli, Massimo. / Effects of octreotide treatment on the proliferation and apoptotic index of GH-secreting pituitary adenomas. In: Journal of Clinical Endocrinology and Metabolism. 2001 ; Vol. 86, No. 11. pp. 5194-5200.
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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 end-labeling 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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AU - Losa, Marco

AU - Ciccarelli, Enrica

AU - Mortini, Pietro

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AU - Gaia, Daniela

AU - Faccani, Giuliano

AU - Papotti, Mauro

AU - Mangili, Francesca

AU - Terreni, Maria Rosa

AU - Camanni, Franco

AU - Giovanelli, Massimo

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