Exp Clin Endocrinol Diabetes 2018; 126(03): 168-175
DOI: 10.1055/s-0042-107243
Article
© Georg Thieme Verlag KG Stuttgart · New York

Preoperative Somatostatin Analogue Treatment Might Trigger Apoptosis and Autophagy in Tumor Tissues of Patients with Acromegaly: A Pilot Study

F. K. Dagistanli*
1   Department of Medical Biology, Cerrahpasa Medical School, Istanbul University, Istanbul, Turkey
,
H. M. Ozkaya*
2   Department of Endocrinology and Metabolism, Cerrahpasa Medical School, Istanbul University, Istanbul, Turkey
,
B. Kucukyoruk
3   Department of Neurosurgery, Cerrahpasa Medical School, Istanbul University, Istanbul, Turkey
,
H. Biceroglu
3   Department of Neurosurgery, Cerrahpasa Medical School, Istanbul University, Istanbul, Turkey
,
D. Metin
1   Department of Medical Biology, Cerrahpasa Medical School, Istanbul University, Istanbul, Turkey
,
N. Gazioglu
3   Department of Neurosurgery, Cerrahpasa Medical School, Istanbul University, Istanbul, Turkey
5   Pituitary Center, Istanbul University, Istanbul, Turkey
,
B. Oz
4   Department of Pathology, Cerrahpasa Medical School, Istanbul University, Istanbul, Turkey
,
P. Kadioglu
2   Department of Endocrinology and Metabolism, Cerrahpasa Medical School, Istanbul University, Istanbul, Turkey
5   Pituitary Center, Istanbul University, Istanbul, Turkey
,
M. Ozturk
1   Department of Medical Biology, Cerrahpasa Medical School, Istanbul University, Istanbul, Turkey
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Publikationsverlauf

received 23. Januar 2016
first decision 29. März 2016

accepted 15. April 2016

Publikationsdatum:
20. Juni 2016 (online)

Abstract

Objective: To evaluate the effect of preoperative somatostatin analog (SRL) treatment on proteins associated with apoptosis and autophagy in patients with acromegaly and to determine factors correlating with these parameters.

Methods: Ex-vivo tumor samples of 11 SRL-treated and 9 SRL-untreated patients were retrospectively included in the study. Apoptotic and autophagic proteins were determined via immunohistochemical staining and apoptosis was evaluated via in situ DNA end labeling (TUNEL).

Results: TUNEL, caspase-3, and ATG-5 immunopositivity was significantly increased (p<0.01, p=0.01, p=0.01, respectively), survivin and beclin-1 immunopositivity was significantly decreased (p=0.03, p=0.02, respectively) in SRL-treated patients as compared with SRL-untreated controls. Ki-67 index was decreased significantly in the SRL-treated group (p=0.01). Significant positive correlations were detected between TUNEL and caspase-3 immunopositivity (r=0.577, p<0.01), and between survivin and beclin-1 immunopositivity (r=0.503, p=0.03). Age at diagnosis, preoperative GH, IGF-1 levels, tumor size, and invasion status were not found to affect TUNEL positivity nor did they correlate with caspase-3, survivin, beclin-1, ATG-5 immunopositivity (p>0.05 for all). Preoperative SRL treatment was the only factor that had a significant effect on TUNEL positivity (adjusted R2=0.39, p=0.02). Preoperative treatment duration was positively correlated with TUNEL and caspase-3 immunopositivity (r=0.526, p=0.02; r=0.475, p=0.04, respectively) and negatively correlated with survivin immunopositivity (r=−0.533, p=0.01).

Conclusions: Somatostatin analog treatment might induce apoptosis, increase autophagy, and decrease cell proliferation in GH-secreting adenomas. Also, proteins related to cross-talk between autophagy and apoptosis are upregulated after SRL treatment.

* Fatma Kaya Dagistanli and Hande Mefkure Ozkaya equally contributed to this study.