Predictive and prognostic significance of tumour subtype, SSTR1-5 and e-cadherin expression in a well-defined cohort of patients with acromegaly
Jazyk angličtina Země Velká Británie, Anglie Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
Grantová podpora
NV19-01-00435
Ministerstvo Zdravotnictví Ceské Republiky
PubMed
33491286
PubMed Central
PMC7933931
DOI
10.1111/jcmm.16173
Knihovny.cz E-zdroje
- Klíčová slova
- PITNET, acromegaly, pituitary neoplasm, somatostatin receptor,
- MeSH
- akromegalie komplikace genetika metabolismus MeSH
- biologické markery MeSH
- dospělí MeSH
- imunohistochemie MeSH
- kadheriny genetika MeSH
- klinické rozhodování MeSH
- kombinovaná terapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- management nemoci MeSH
- mladý dospělý MeSH
- nádory hypofýzy diagnóza etiologie terapie MeSH
- prognóza MeSH
- protein - isoformy MeSH
- receptory somatostatinu genetika metabolismus MeSH
- regulace genové exprese * MeSH
- ROC křivka MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- biologické markery MeSH
- kadheriny MeSH
- protein - isoformy MeSH
- receptory somatostatinu MeSH
In somatotroph pituitary tumours, somatostatin analogue (SSA) therapy outcomes vary throughout the studies. We performed an analysis of cohort of patients with acromegaly from the Czech registry to identify new prognostic and predictive factors. Clinical data of patients were collected, and complex immunohistochemical assessment of tumour samples was performed (SSTR1-5, dopamine D2 receptor, E-cadherin, AIP). The study included 110 patients. In 31, SSA treatment outcome was evaluated. Sparsely granulated tumours (SGST) differed from the other subtypes in expression of SSTR2A, SSTR3, SSTR5 and E-cadherin and occurred more often in young. No other clinical differences were observed. Trouillas grading system showed association with age, tumour size and SSTR2A expression. Factors significantly associated with SSA treatment outcome included age, IGF1 levels, tumour size and expression of E-cadherin and SSTR2A. In the group of SGST, poor SSA response was observed in younger patients with larger tumours, lower levels of SSTR2A and higher Ki67. We observed no relationship with expression of other proteins including AIP. No predictive value of E-cadherin was observed when tumour subtype was considered. Multiple additional factors apart from SSTR2A expression can predict treatment outcome in patients with acromegaly.
1st Internal Clinic Louis Pasteur University Hospital Kosice Slovakia
Bioptical Laboratory Ltd Plzen Czech Republic
Department of Pathology Faculty of Medicine Charles University Plzen Czech Republic
Department of Pathology Military University Hospital Prague Prague Czech Republic
National Institute of Endocrinology and Diabetology Lubochňa Slovakia
Zobrazit více v PubMed
Asa SL, Casar‐Borota O, Chanson P, et al. From pituitary adenoma to pituitary neuroendocrine tumor (PitNET): an International Pituitary Pathology Club proposal. Endocr Relat Cancer. 2017;24(4):C5‐C8. PubMed
Osamura RY, Kajiya H, Takei M, et al. Pathology of the human pituitary adenomas. Histochem Cell Biol. 2008;130(3):495‐507. PubMed PMC
Gadelha MR, Wildemberg LE, Bronstein MD, Gatto F, Ferone D. Somatostatin receptor ligands in the treatment of acromegaly. Pituitary. 2017;20(1):100‐108. PubMed
Bevan JS. Clinical review: The antitumoral effects of somatostatin analog therapy in acromegaly. J Clin Endocrinol Metab. 2005;90(3):1856‐1863. PubMed
Colao A, Auriemma RS, Pivonello R. The effects of somatostatin analogue therapy on pituitary tumor volume in patients with acromegaly. Pituitary. 2016;19(2):210‐221. PubMed PMC
Taboada GF, Luque RM, Neto LV, et al. Quantitative analysis of somatostatin receptor subtypes (1–5) gene expression levels in somatotropinomas and correlation to in vivo hormonal and tumor volume responses to treatment with octreotide LAR. Eur J Endocrinol. 2008;158(3):295‐303. PubMed
Wildemberg LE, Neto LV, Costa DF, et al. Low somatostatin receptor subtype 2, but not dopamine receptor subtype 2 expression predicts the lack of biochemical response of somatotropinomas to treatment with somatostatin analogs. J Endocrinol Invest. 2013;36(1):38‐43. PubMed
Gatto F, Feelders RA, van der Pas R, et al. Immunoreactivity score using an anti‐sst2A receptor monoclonal antibody strongly predicts the biochemical response to adjuvant treatment with somatostatin analogs in acromegaly. J Clin Endocrinol Metab. 2013;98(1):E66‐E71. PubMed
Brzana J, Yedinak CG, Gultekin SH, Delashaw JB, Fleseriu M. Growth hormone granulation pattern and somatostatin receptor subtype 2A correlate with postoperative somatostatin receptor ligand response in acromegaly: a large single center experience. Pituitary. 2013;16(4):490‐498. PubMed
Jaffrain‐Rea ML, Rotondi S, Turchi A, et al. Somatostatin analogues increase AIP expression in somatotropinomas, irrespective of Gsp mutations. Endocr Relat Cancer. 2013;20(5):753‐766. PubMed
Fougner SL, Lekva T, Borota OC, Hald JK, Bollerslev J, Berg JP. The expression of E‐cadherin in somatotroph pituitary adenomas is related to tumor size, invasiveness, and somatostatin analog response. J Clin Endocrinol Metab. 2010;95(5):2334‐2342. PubMed
Venegas‐Moreno E, Flores‐Martinez A, Dios E, et al. E‐cadherin expression is associated with somatostatin analogue response in acromegaly. J Cell Mol Med. 2019;23(5):3088‐3096. PubMed PMC
Iacovazzo D, Carlsen E, Lugli F, et al. Factors predicting pasireotide responsiveness in somatotroph pituitary adenomas resistant to first‐generation somatostatin analogues: an immunohistochemical study. Eur J Endocrinol. 2016;174(2):241‐250. PubMed
Trouillas J, Roy P, Sturm N, et al. A new prognostic clinicopathological classification of pituitary adenomas: a multicentric case‐control study of 410 patients with 8 years post‐operative follow‐up. Acta Neuropathol. 2013;126(1):123‐135. PubMed
Villa C, Vasiljevic A, Jaffrain‐Rea ML, et al. A standardised diagnostic approach to pituitary neuroendocrine tumours (PitNETs): a European Pituitary Pathology Group (EPPG) proposal. Virchows Arch. 2019;475(6):687‐692. PubMed
Lloyd RVOR, Klöppel G, Rosai J (Eds). WHO Classification of Tumours of Endocrine Organs, 4th edn. Lyon, France: IARC; 2017. 355 p.
Syro LV, Rotondo F, Serna CA, Ortiz LD, Kovacs K. Pathology of GH‐producing pituitary adenomas and GH cell hyperplasia of the pituitary. Pituitary. 2017;20(1):84‐92. PubMed
Mori R, Inoshita N, Takahashi‐Fujigasaki J, et al. Clinicopathological features of growth hormone‐producing pituitary adenomas in 242 acromegaly patients: classification according to hormone production and cytokeratin distribution. ISRN Endocrinol. 2013;2013:723432. PubMed PMC
Larkin S, Reddy R, Karavitaki N, Cudlip S, Wass J, Ansorge O. Granulation pattern, but not GSP or GHR mutation, is associated with clinical characteristics in somatostatin‐naive patients with somatotroph adenomas. Eur J Endocrinol. 2013;168(4):491‐499. PubMed
Kiseljak‐Vassiliades K, Carlson NE, Borges MT, et al. Growth hormone tumor histological subtypes predict response to surgical and medical therapy. Endocrine. 2015;49(1):231‐241. PubMed PMC
Chinezu L, Vasiljevic A, Jouanneau E, et al. Expression of somatostatin receptors, SSTR2A and SSTR5, in 108 endocrine pituitary tumors using immunohistochemical detection with new specific monoclonal antibodies. Hum Pathol. 2014;45(1):71‐77. PubMed
Kiseljak‐Vassiliades K, Xu M, Mills TS, et al. Differential somatostatin receptor (SSTR) 1–5 expression and downstream effectors in histologic subtypes of growth hormone pituitary tumors. Mol Cell Endocrinol. 2015;417:73‐83. PubMed PMC
Mayr B, Buslei R, Theodoropoulou M, Stalla GK, Buchfelder M, Schofl C. Molecular and functional properties of densely and sparsely granulated GH‐producing pituitary adenomas. Eur J Endocrinol. 2013;169(4):391‐400. PubMed
Obari A, Sano T, Ohyama K, et al. Clinicopathological features of growth hormone‐producing pituitary adenomas: difference among various types defined by cytokeratin distribution pattern including a transitional form. Endocr Pathol. 2008;19(2):82‐91. PubMed
Bakhtiar Y, Hirano H, Arita K, et al. Relationship between cytokeratin staining patterns and clinico‐pathological features in somatotropinomae. Eur J Endocrinol. 2010;163(4):531‐539. PubMed
Neou M, Villa C, Armignacco R, et al. Pangenomic classification of pituitary neuroendocrine tumors. Cancer Cell. 2020;37(1):123‐34 e5. PubMed
Venegas‐Moreno E, Vazquez‐Borrego MC, Dios E, et al. Association between dopamine and somatostatin receptor expression and pharmacological response to somatostatin analogues in acromegaly. J Cell Mol Med. 2018;22(3):1640‐1649. PubMed PMC
Neto LV, Machado EDO, Luque RM, et al. Expression analysis of dopamine receptor subtypes in normal human pituitaries, nonfunctioning pituitary adenomas and somatotropinomas, and the association between dopamine and somatostatin receptors with clinical response to octreotide‐LAR in acromegaly. J Clin Endocrinol Metab. 2009;94(6):1931‐1937. PubMed PMC
Cuevas‐Ramos D, Carmichael JD, Cooper O, et al. A structural and functional acromegaly classification. J Clin Endocrinol Metab. 2015;100(1):122‐131. PubMed PMC
Ben‐Shlomo A, Melmed S. Pituitary somatostatin receptor signaling. Trends Endocrinol Metab. 2010;21(3):123‐133. PubMed PMC
Ozkaya HM, Comunoglu N, Sayitoglu M, et al. Germline mutations of aryl hydrocarbon receptor‐interacting protein (AIP) gene and somatostatin receptor 1–5 and AIP immunostaining in patients with sporadic acromegaly with poor versus good response to somatostatin analogues. Pituitary. 2018;21(4):335‐346. PubMed
Fougner SL, Borota OC, Berg JP, Hald JK, Ramm‐Pettersen J, Bollerslev J. The clinical response to somatostatin analogues in acromegaly correlates to the somatostatin receptor subtype 2a protein expression of the adenoma. Clin Endocrinol (Oxf). 2008;68(3):458‐465. PubMed
Fougner SL, Casar‐Borota O, Heck A, Berg JP, Bollerslev J. Adenoma granulation pattern correlates with clinical variables and effect of somatostatin analogue treatment in a large series of patients with acromegaly. Clin Endocrinol (Oxf). 2012;76(1):96‐102. PubMed
Rocheville M, Lange DC, Kumar U, Patel SC, Patel RC, Patel YC. Receptors for dopamine and somatostatin: formation of hetero‐oligomers with enhanced functional activity. Science. 2000;288(5463):154‐157. PubMed
Grant M, Alturaihi H, Jaquet P, Collier B, Kumar U. Cell growth inhibition and functioning of human somatostatin receptor type 2 are modulated by receptor heterodimerization. Mol Endocrinol. 2008;22(10):2278‐2292. PubMed PMC
Daly A, Cano DA, Venegas E, et al. AIP and MEN1 mutations and AIP immunohistochemistry in pituitary adenomas in a tertiary referral center. Endocr Connect. 2019;8(4):338‐348. PubMed PMC
Uhlen M, Fagerberg L, Hallstrom BM, et al. Proteomics. Tissue‐based map of the human proteome. Science. 2015;347(6220):1260419. PubMed
Human Protein Atlas available from http://www.proteinatlas.org