A Novel Expression Profile of Cell Cycle and DNA Repair Proteins in Nonfunctioning Pituitary Adenomas Derya Metin-Armagan 1 & Nil Comunoglu 2 & Gulay Bulut 3 & Pinar Kadioglu 4 & Hiraku Kameda 5 & Nurperi Gazioglu 6 & Necmettin Tanriover 7 & Melek Ozturk 1 # Springer Science+Business Media, LLC, part of Springer Nature 2019 Abstract The molecular mechanisms underlying the formation of nonfunctioning pituitary adenomas (NFAs) are largely unknown. In this study, we aimed to understand the relationship between NFAs and functional pituitary adenomas and the possible role of proteins involved in cell cycle, senescence, and DNA damage control mechanisms in the etiology of NFA. We analyzed pATM-S1981, pRb-S608, Rb, pE2F1-S364, p16, E2F1, p73, cyclin D1, and CHEK2 protein expression (in a group of 20 patients with acromegaly, 18 patients with Cushing’ s disease (CD), and 29 NFA patients) by immunohistochemistry and their relevant mRNA expression by qRT-PCR (in a group of 7 patients with acromegaly, 7 patients with CD, and 7 NFA patients). The clinical and histopathological results on the patients were statistically evaluated. pE2F1-S364 protein expression in the CD group was significantly lower than that in the NFA and acromegaly groups (p = 0.025, p = 0.034, respectively). However, the expression of the p16 protein was lower than in the NFA group than in the CD and acromegaly groups (p = 0.030, p = 0.033, respectively), and E2F1 protein expression was significantly higher in the NFA group than in the CD group (p = 0.025). p73 protein expression in patients with acromegaly was significantly higher (p = 0.031) than that in the CD group. CHEK2 mRNA expression in the CD group was significantly higher than that in the acromegaly group (p = 0.012). The selective and tumor-specific associations between E2F1, pE2F1-S364, CHEK2, and p73 mRNA and protein levels indicate their involvement in pituitary adenoma formation in NFA, CD, and acromegaly patients. Keywords Nonfunctioning pituitary adenomas . E2F1 . pE2F1-S364 . CHEK2 . p73 . RB . p16 Introduction Pituitary adenomas constitute 15% of intracranial tumors [1]. Pituitary tumors are monoclonal benign adenomas that are formed by the proliferation of a single precursor cell rather than by hyperplastic growth. These monoclonal adenomas secrete specific hormones reflecting the origin of the differen- tiated cell [ 2 ]. Growth hormone (GH)-secreting somatotropinomas cause gigantism or acromegaly. Corticotropic tumors that secrete adrenocorticotropic hor- mone (ACTH) result in Cushing ’ s disease (CD). Additionally, gonadotrophs cause the formation of adenomas, but they secrete small amounts of luteinizing hormone (LH) or follicle-stimulating hormone (FSH), and most of them are clinically nonfunctioning adenomas (NFAs) [3]. Clinically NFAs are completely asymptomatic and difficult to diagnose in the early stages of the disease. Intracranial magnetic reso- nance imaging or computed tomography can detect NFAs during the investigation of significant pituitary insufficiency * Melek Ozturk mozturk@istanbul.edu.tr 1 Department of Medical Biology, Cerrahpasa Medical School, Istanbul University-Cerrahpasa, Istanbul, Turkey 2 Department of Pathology, Cerrahpasa Medical School, Istanbul University-Cerrahpasa, Istanbul, Turkey 3 Department of Molecular Biology and Genetics, Faculty of Engineering and Natural Sciences, Bahçeşehir University, Istanbul, Turkey 4 Department of Endocrinology and Metabolism, Cerrahpasa Medical School, Istanbul University-Cerrahpasa, Cerrahpasa, Istanbul, Turkey 5 Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan 6 Department of Neurosurgery, Istanbul Bilim University, Istanbul, Turkey 7 Department of Neurosurgery, Cerrahpasa Medical School, Istanbul University- Cerrahpasa, Istanbul, Turkey Endocrine Pathology https://doi.org/10.1007/s12022-019-09598-x