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



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).



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).



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.
Department of Medical Biology, Cerrahpasa Medical School, Istanbul University, Istanbul, Turkey.
F K
FK
Dagistanli
Department of Endocrinology and Metabolism, Cerrahpasa Medical School, Istanbul University, Istanbul, Turkey.
H M
HM
Ozkaya
Department of Neurosurgery, Cerrahpasa Medical School, Istanbul University, Istanbul, Turkey.
B
B
Kucukyoruk
Department of Neurosurgery, Cerrahpasa Medical School, Istanbul University, Istanbul, Turkey.
H
H
Biceroglu
Department of Medical Biology, Cerrahpasa Medical School, Istanbul University, Istanbul, Turkey.
D
D
Metin
Department of Neurosurgery, Cerrahpasa Medical School, Istanbul University, Istanbul, Turkey.|Pituitary Center, Istanbul University, Istanbul, Turkey.
N
N
Gazioglu
Department of Pathology, Cerrahpasa Medical School, Istanbul University, Istanbul, Turkey.
B
B
Oz
Department of Endocrinology and Metabolism, Cerrahpasa Medical School, Istanbul University, Istanbul, Turkey.|Pituitary Center, Istanbul University, Istanbul, Turkey.
P
P
Kadioglu
Department of Medical Biology, Cerrahpasa Medical School, Istanbul University, Istanbul, Turkey.
M
M
Ozturk
D000172:Acromegaly / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D000236:Adenoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D000328:Adult; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D003430:Cross-Sectional Studies; D005260:Female; D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011300:Preoperative Care; D012189:Retrospective Studies; D013004:Somatostatin / Q000008:administration & dosage / Q000032:analysis / Q000494:pharmacology*
D013004:Somatostatin