Role of AGR2 Expression in Specimens from Pituitary Adenoma Tissue on Tumor Behavior

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.