Immunohistochemical detection of prolactin in clinically non-functioning pituitary adenomas
, 1, 1, 1, 1
Abstract
Introduction. Approximately one third of pituitary adenomas are manifested neither by specific symptoms of hormone overproduction nor by elevated blood levels of pituitary hormones. However, these tumours, diagnosed before surgical intervention as clinically non-functioning pituitary adenomas (CNFPAs) express in majority different pituitary hormones, as can be revealed by means of immunohistochemical examination. One of the pituitary hormones which may be expressed in CNFPAs is prolactin (PRL) but the clinical and pathological data on this condition are very scarce. Material and methods. Sixty two pituitary adenomas, diagnosed before surgery as CNFPAs, were immunoassayed with antibodies against PRL, growth hormone (GH), luteinizing hormone (LH), follicle stimulating hormone (FSH), thyrotropin (TSH), alpha subunit (alpha-SU), corticotropin (ACTH) and dopamine receptor type 2. In a proportion of the patients the presurgical concentrations of insulin-like growth factor 1 (IGF-1) were estimated by means of enzyme-amplified chemiluminescence assay. Results. Twenty-three (37.1%) of the examined CNFPAs presented the positive immunoreaction with anti-PRL antibody. Most cases concerned women. Only in two cases (one woman and one man), PRL was the unique hormone expressed in the tumour. In the remaining adenomas PRL immunopositivity was accompanied by GH expression — 17, LH or free bLH — 13, FSH — 2, free a subunit — 4 or by ACTH — 5 tumours. Seven (30.43%) of them were recurrent in comparison with 12.8% PRL-immunonegative recurrent CNFPAs. Dopamine receptors were positively immunostained in all the investigated PRL-immunopositive and all PRL-immunonegative adenomas.
Conclusions. Our data confirm the observations that monohormonal silent prolactinomas are very rare but frequently silent PRL often co-expressed with GH or LH. Although in the whole population of patients with CNFPAs both sexes are equally represented, in the case of silent prolactinomas the female sex is prevalent. The observation of the higher rate of recurrent tumours within PRL-immunopositive adenomas versus PRL-immunonegative CNFPAs has to be confirmed on the larger material.
Keywords: clinically non-functioning pituitary adenomasimmunohistochemistrysilent prolactinomaGHLHdopamine receptorsinsulin-like growth factor-1
References
- Wade AN, Baccon J, Grady MS, et al. Clinically silent somatotroph adenomas are common. Eur J Endocrinol. 2011; 165(1): 39–44.
- Mayson SE, Snyder PJ, Mayson SE, et al. Silent (clinically nonfunctioning) pituitary adenomas. J Neurooncol. 2014; 117(3): 429–436.
- Mayson SE, Snyder PJ. Silent pituitary adenomas. Endocrinol Metab Clin North Am. 2015; 44(1): 79–87.
- Mercado M, Melgar V, Salame L, et al. Clinically non-functioning pituitary adenomas: Pathogenic, diagnostic and therapeutic aspects. Endocrinol Diabetes Nutr. 2017; 64(7): 384–395.
- Manojlovic-Gacic E, Engström BE, Casar-Borota O. Histopathological classification of non-functioning pituitary neuroendocrine tumors. Pituitary. 2018; 21(2): 119–129.
- Ntali G, Wass JA. Epidemiology, clinical presentation and diagnosis of non-functioning pituitary adenomas. Pituitary. 2018; 21(2): 111–118.
- Drummond J, Roncaroli F, Grossman AB, et al. Clinical and Pathological Aspects of Silent Pituitary Adenomas. J Clin Endocrinol Metab. 2019; 104(7): 2473–2489.
- Pawlikowski M, Kunert-Radek J, Radek A. Gonadotropinoma - a frequent subtype of the pituitary adenoma. Endokrynol Pol. 2000; 51: 77–81.
- Asa SL, Ezzat S. Gonadotrope Tumors. Prog Mol Biol Transl Sci. 2016; 143: 187–210.
- Pawlikowski Łódź M, Jaranowska M, Fryczak J, et al. Blood serum concentrations of gonadotropins and α-subunit in patients with gonadotropinomas in relation to the immunoreactivity of pituitary adenoma. Endokrynol Pol. 2018; 69(5): 526–529.
- Reincke M, Allolio B, Saeger W, et al. A pituitary adenoma secreting high molecular weight adrenocorticotropin without evidence of Cushing's disease. J Clin Endocrinol Metab. 1987; 65(6): 1296–1300.
- Iino K, Oki Y, Matsushita F, et al. Immunohistochemical properties of silent corticotroph adenoma and Cushing's disease. Pituitary. 2007; 10(1): 35–45.
- Pawlikowski M, Kunert-Radek J, Radek M. “Silent” corticotropinoma. Neuro Endocrinol Lett. 2008; 29(3): 347–350.
- Guttenberg KB, Mayson SE, Sawan C, et al. Prevalence of clinically silent corticotroph macroadenomas. Clin Endocrinol (Oxf). 2016; 85(6): 874–880.
- Kovacs K, Lloyd R, Horvath E, et al. Silent somatotroph adenomas of the human pituitary. Amer J Pathol. 1989; 134: 345–353.
- Trouillas J, Sassolas G, Guigard MP, et al. Somatotropic adenomas without acromegaly. Pathol Res Pract. 1991; 187(8): 943–949.
- Yamada S, Sano T, Stefaneanu L, et al. Endocrine and morphological study of a clinically silent somatotroph adenoma of the human pituitary. J Clin Endocrinol Metab. 1993; 76(2): 352–356.
- Naritaka H, Kameya T, Sato Y, et al. Morphological characterization and subtyping of silent somatotroph adenomas. Pituitary. 1999; 1(3-4): 233–241.
- Matsuno A, Itoh J, Itoh Y, et al. Histopathological analyses of silent pituitary somatotroph adenomas using immunohistochemistry, in situ hybridization and confocal laser scanning microscopic observation. Pathol Res Pract. 2001; 197(1): 13–20.
- Pawlikowski M, Kuta J, Fuss-Chmielewska J, et al. 'Silent' somatotropinoma. Endokrynol Pol. 2012; 63(2): 88–91.
- Pawlikowski M, Pisarek H, Jaranowska M, et al. Endokrynol Pol. 2016; 67(5): 515–518.
- Saeger W, Lüdecke DK, Buchfelder M, et al. Pathohistological classification of pituitary tumors: 10 years of experience with the German Pituitary Tumor Registry. Eur J Endocrinol. 2007; 156(2): 203–216.
- Korol P, Jaranowska M, Pawlikowski M. Immunohistochemical demonstration of LH/CG receptors in non-neoplastic human adrenal cortex and adrenocortical tumors. Folia Histochem Cytobiol. 2019; 57(1): 23–27.
- Mavrakis AN, Tritos NA. Diagnostic and therapeutic approach to pituitary incidentalomas. Endocr Pract. 2004; 10(5): 438–444.
- Kaptain GJ, Simmons NE, Alden TD, et al. Estrogen receptors in prolactinomas: a clinico-pathological study. Pituitary. 1999; 1(2): 91–98.
- Diri H, Ozaslan E, Kurtsoy A, et al. Is Positive Staining of Non-Functioning Pituitary Adenomas for Luteinizing Hormone Associated with a Poor Prognosis? Turk Neurosurg. 2017; 27(1): 8–13.
- Vieira Ne, Widemberg LE, Moraes AB, et al. Dopamine receptor subtype 2 expression profile in nonfunctioning pituitary adenomas and in vivo response to cabergoline therapy. Clin Endocrinol (Oxf). 2015; 82: 739–746.
- Pivonello R, Matrone C, Filippella M, et al. Dopamine receptor expression and function in clinically nonfunctioning pituitary tumors: comparison with the effectiveness of cabergoline treatment. J Clin Endocrinol Metab. 2004; 89(4): 1674–1683.
- Pawlikowski M. Immunohistochemical detection of dopamine D2 receptors in human pituitary adenomas. Folia Histochem Cytobiol. 2010; 48(3): 394–397.
- Cooper O, Greenman Y. Dopamine Agonists for Pituitary Adenomas. Frontiers in Endocrinology. 2018; 9.
- Batista RL, Musolino NRC, Cescato VAS, et al. Cabergoline in the Management of Residual Nonfunctioning Pituitary Adenoma: A Single-Center, Open-Label, 2-Year Randomized Clinical Trial. Am J Clin Oncol. 2019; 42(2): 221–227.
