ORIGINAL ARTICLE
Role of AGR2 Expression in Specimens from Pituitary Adenoma Tissue on Tumor Behavior
Hipofiz Adenom Doku Örneklerinde AGR2 Ekspresyonunun Tümör Davranışı Üzerine Etkisi
Received Date : 10 Jun 2020
Accepted Date : 25 Sep 2020
Available Online : 16 Oct 2020
Sema ÇİFTÇİ DOĞANŞEN, Ömür GÜNALDI*, Ayla Solmaz AVCIKURT**, Barış ÇOLLUOĞLU*, İlhan YILMAZ*, Meral MERT, Osman TANRIVERDİ*
Department of Endocrinology and Metabolism, University of Health Sciences, Bakırköy Dr. Sadi Konuk Training and Research Hospital, İstanbul, TURKEY
*Department of Neurosurgery, University of Health Sciences, Bakırköy Prof. Dr. Mazhar Osman Training and Research Hospital for Neurology, Neurosurgery and Psychiatry,
**Department of Medical Biology, Balıkesir University Faculty of Medicine, Balıkesir, TURKEY
Doi: 10.25179/tjem.2020-76663 - Makale Dili: EN
Turk J Endocrinol Metab. 2020;24:293-299
ABSTRACT
Objective: To investigate the anterior gradient 2 (AGR2) mRNA
expression, which performs various cellular functions such as cell
migration, differentiation, and proliferation in tissue specimens
from pituitary adenomas. Material and Methods: A total of 44
pituitary adenoma specimens (20 female/24 male) from patients,
and ten normal brain tissues (5 female/5 male) operated for epilepsy
surgery (control group) were included in the study. Specimens
were stored at -80 °C throughout the study. Molecular
assessment of pituitary adenomas and control brain tissues was
performed to quantify mRNA expression of AGR2using real-time
PCR. Distribution of AGR2 mRNA expression levels was evaluated
according to pituitary adenoma subtypes, tumor aggressiveness,
or invasiveness. Results: Expression levels of AGR2 mRNA in corticotroph
(n=5) and somatotroph adenomas (n=14) were higher
compared to control brain tissues (p=0.045 and p=0.005, respectively);
however, expression levels of AGR2 mRNA in lactotroph
(n=3), gonadotroph (n=14), and non-secretory adenomas (n=7)
were similar to the control brain tissues. The thyrotroph adenoma
(n=1) was not included in the analysis. Expression levels of AGR2
mRNA were similar in female and male patients. The expression
levels of the AGR2 mRNA were higher in non-invasive tumors
(n=20) than invasive tumors (n=24) (p=0.001), and in the nonaggressive
tumors (n=27) than aggressive tumors (n=17)
(p=0.018). A negative correlation between expression levels of
AGR2 mRNA and Ki-67 labeling index (r=-0.328; p=0,029) was
obtained. However, no correlation was found between the expression
levels of AGR2 mRNA and age or maximum tumor diameter.
Conclusion: AGR2 expression is inversely correlated to invasiveness
and aggressiveness, independently from age and sex in pituitary
adenomas.
Keywords: Anterior gradient 2; AGR2; pituitary adenoma; aggressiveness; invasiveness; somatotroph adenoma
ÖZET
Amaç: Migrasyon, farklılaşma ve proliferasyon gibi çeşitli hücresel
görevleri olan anterior gradient 2 (AGR2) expresyonunun hipofiz
adenom doku örneklerinde değerlendirilmesi. Gereç ve Yöntemler:
Bu çalışmaya, 44 hastanın (20 kadın/24 erkek) hipofiz adenom
doku örnekleri ve epilepsi cerrahisi uygulanan 10 hastanın (5
kadın/5 erkek) da normal beyin dokusu örnekleri kontrol grubu olarak
kabul edilerek dâhil edilmiştir. Tüm doku örnekleri çalışılana
kadar -80°C’de saklanmıştır. Dokularda AGR2 mRNA ekspresyonu
real-time PCR kullanılarak kullanılarak değerlendirilmiştir. Hipofizer
adenomunun subtipi, tümörün agresifliği ve invazivliğine göre
AGR2 mRNA ekspresyonunun dağılımına bakılmıştır. Bulgular:
AGR2 mRNA ekspresyonu kortikotrop adenomlarda (n=5) ve somatotrop
adenomlarda (n=14), kontrol beyin dokusundan daha
yüksekti (sırasıyla, p=0,045 ve p=0,005), bununla birlikte lactotrop
adenomlarda (n=3), gonadotrop adenomalarda (n=14) ve nonsekretuar
adenomlarda (n=7) kontrol beyin dokusuna göre benzer
idi, tirotrop adenomlar ise (n=1) hesaplamalara dâhil edilmemiştir.
AGR2 mRNA ekspresyonu kadın ve erkeklerde benzerdir. İnvaziv
olmayanlarda (n=20), invasiv tümörlerden (n=24), agresif olmayanlarda
(n=27) ise agresif tümörlerden (n=17) AGR2 mRNA ekspresyonu
anlamlı derecede yüksekti (sırasıyla, p=0,001 ve
p=0,018). AGR2 mRNA ekspresyonu ile Ki-67 labeling index arasında
bir negatif korelasyon (r=-0,328; p=0,029) saptanırken yaş
ve maksimum tümör boyutu arasında bir korelasyon saptanmadı.
Sonuç: AGR2 ekspresyonu yaş ve cinsiyetten bağımsız olarak hipofiz
adenomlarının agresifliği ve invazivliği ile ters orantılıdır.
Anahtar Kelimeler: Anterior gradient 2; AGR2; hipofiz adenoma; agresiflik; invazivlik; somatotrof adenom
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