title: Locally produced estrogen through aromatization might enhance tissue expression of pituitary tumor transforming gene and fibroblast growth factor 2 in growth hormone-secreting adenomas.
abstract: Aromatase, a key enzyme in local estrogen synthesis, is expressed in different pituitary tumors including growth hormone (GH)-secreting adenomas. We aimed to evaluate aromatase, estrogen receptor α (ERα), estrogen receptor β (ERβ), pituitary tumor transforming gene (PTTG), and fibroblast growth factor 2 (FGF2) expressions in GH-secreting adenomas, and investigate their correlation with clinical, pathologic, and radiologic parameters. This cross-sectional study was conducted in a tertiary center in Turkey. Protein expressions were determined via immunohistochemical staining in ex vivo tumor samples of 62 patients with acromegaly and ten normal pituitary tissues. Concordantly increased aromatase, PTTG, and FGF2 expressions were detected in the tumor samples as compared with controls (p < 0.001 for all). None of the tumors expressed ERα while ERβ was detected only in mixed somatotroph adenomas. Aromatase, ERβ, PTTG expressions were not significantly different between patients with and without remission (p > 0.05 for all). FGF2 expression was significantly higher in patients without postoperative and late remission (p = 0.002 and p = 0.012, respectively), with sphenoid bone invasion, optic chiasm compression, and somatostatin analog resistance (p = 0.005, p = 0.033, and p = 0.013, respectively). Aromatase, PTTG and FGF2 expressions were positively correlated with each other (r = 0,311, p = 0.008 for aromatase, FGF2; r = 0.380, p = 0.001 for aromatase, PTTG; r = 0.400, p = 0.001 for FGF2, PTTG). PTTG-mediated FGF2 upregulation is associated with more aggressive tumor features in patients with acromegaly. Also, locally produced estrogen through aromatization might have a role in this phenomenon.
authors.affiliation: Department of Endocrinology and Metabolism, Cerrahpasa Medical School, University of Istanbul, Cerrahpasa, 34303, Istanbul, Turkey.
authors.forename: Hande Mefkure
authors.initials: HM
authors.lastname: Ozkaya
authors.affiliation: Department of Pathology, Cerrahpasa Medical School, University of Istanbul, Istanbul, Turkey.
authors.forename: Nil
authors.initials: N
authors.lastname: Comunoglu
authors.affiliation: Department of Endocrinology and Metabolism, Cerrahpasa Medical School, University of Istanbul, Cerrahpasa, 34303, Istanbul, Turkey.
authors.forename: Fatma Ela
authors.initials: FE
authors.lastname: Keskin
authors.affiliation: Department of Pathology, Cerrahpasa Medical School, University of Istanbul, Istanbul, Turkey.
authors.forename: Buge
authors.initials: B
authors.lastname: Oz
authors.affiliation: Department of Endocrinology and Metabolism, Cerrahpasa Medical School, University of Istanbul, Cerrahpasa, 34303, Istanbul, Turkey.
authors.forename: Ozlem Asmaz
authors.initials: OA
authors.lastname: Haliloglu
authors.affiliation: Department of Neurosurgery, Cerrahpasa Medical School, University of Istanbul, Istanbul, Turkey.
authors.forename: Necmettin
authors.initials: N
authors.lastname: Tanriover
authors.affiliation: Department of Neurosurgery, Cerrahpasa Medical School, University of Istanbul, Istanbul, Turkey.
authors.forename: Nurperi
authors.initials: N
authors.lastname: Gazioglu
authors.affiliation: Department of Endocrinology and Metabolism, Cerrahpasa Medical School, University of Istanbul, Cerrahpasa, 34303, Istanbul, Turkey. kadioglup@yahoo.com.
authors.forename: Pinar
authors.initials: P
authors.lastname: Kadioglu
mesh_terms: D000236:Adenoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000368:Aged; D003430:Cross-Sectional Studies; D004958:Estradiol / Q000096:biosynthesis*; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D053858:Metabolic Networks and Pathways / Q000235:genetics; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D012189:Retrospective Studies; D064249:Securin / Q000235:genetics* / Q000378:metabolism; D014421:Turkey
chemical_list: D064249:Securin; C578002:pituitary tumor-transforming protein 1, human; D016222:Fibroblast Growth Factor 2; D004958:Estradiol
keywords: Acromegaly; Aromatase; Estrogen; FGF2; PTTG protein