Actualización sobre mecanismos de tumorogénesis hipofisaria
DOI:
https://doi.org/10.31053/1853.0605.v78.n4.29189Palabras clave:
hipófisis, adenoma, carcinogénesisResumen
Los adenomas hipofisarios son neoplasias intracraneales que surgen de las células del lóbulo anterior de la glándula, benignos y de crecimiento lento en su gran mayoría. Sin embargo, un pequeño porcentaje puede mostrar un comportamiento clínicamente agresivo y diseminarse localmente y/o a distancia como verdaderas neoplasias malignas. Durante los últimos años, se observó un importante avance en el conocimiento de la biología de los tumores hipofisarios, identificándose mutaciones de las líneas germinal, somática y mecanismos epigenéticos. Objetivo: revisar la bibliografía actualizada sobre los mecanismos que contribuyen a la tumorogénesis hipofisaria. Fuente de datos: se realizó una búsqueda bibliográfica utilizando las bases de datos de MEDLINE (PubMed), LILACS y Google Scholar desde 2010 hasta abril de 2020. Conclusión: El conocimiento e información sobre los mecanismos asociados a la formación de tumores hipofisarios incrementó a lo largo de las últimas décadas, y se reconocen nuevas vías de desarrollo neoplásico. Sin embargo, en la actualidad existen pocos enfoques terapéuticos para actuar específicamente sobre la vía de génesis tumoral subyacente identificada en cada caso.
Descargas
Citas
Melmed S. Mechanisms for pituitary tumorigenesis: the plastic pituitary. J Clin Invest. 2003 Dec;112(11):1603-18. doi: 10.1172/JCI20401.
Würth R, Thellung S, Corsaro A, Barbieri F, Florio T. Experimental Evidence and Clinical Implications of Pituitary Adenoma Stem Cells. Front Endocrinol (Lausanne). 2020 Feb 20;11:54. doi: 10.3389/fendo.2020.00054.
Mantovani G, Giardino E, Treppiedi D, Catalano R, Mangili F, Spada A, Arosio M, Peverelli E. Stem Cells in Pituitary Tumors: Experimental Evidence Supporting Their Existence and Their Role in Tumor Clinical Behavior. Front Endocrinol (Lausanne). 2019 Oct 25;10:745. doi: 10.3389/fendo.2019.00745.
Ezzat S, Asa SL, Couldwell WT, Barr CE, Dodge WE, Vance ML, McCutcheon IE. The prevalence of pituitary adenomas: a systematic review. Cancer. 2004 Aug 1;101(3):613-9. doi: 10.1002/cncr.20412.
Asa SL, Casar-Borota O, Chanson P, Delgrange E, Earls P, Ezzat S, Grossman A, Ikeda H, Inoshita N, Karavitaki N, Korbonits M, Laws ER Jr, Lopes MB, Maartens N, McCutcheon IE, Mete O, Nishioka H, Raverot G, Roncaroli F, Saeger W, Syro LV, Vasiljevic A, Villa C, Wierinckx A, Trouillas J; attendees of 14th Meeting of the International Pituitary Pathology Club, Annecy, France, November 2016. From pituitary adenoma to pituitary neuroendocrine tumor (PitNET): an International Pituitary Pathology Club proposal. EndocrRelat Cancer. 2017 Apr;24(4):C5-C8. doi: 10.1530/ERC-17-0004.
Osamura RY, Grossman AB, Korbonits M, Kovacs K, Lopes MBS, Matsuno A, Trouillas J. Pituitary adenoma. In: Lloyd RV, Osamura RY, Klöppel G, Rosai J, eds. World Health Organization Classification of Tumours of Endocrine Organs. Vol 10. 4th ed. Geneva: International Agency for Cancer Research; 2017:15-19.
Zatelli MC. Pathogenesis of non-functioning pituitary adenomas. Pituitary. 2018 Apr;21(2):130-137. doi: 10.1007/s11102-018-0874-6.
Malumbres M, Barbacid M. Mammalian cyclin-dependent kinases. Trends Biochem Sci. 2005 Nov;30(11):630-41. doi: 10.1016/j.tibs.2005.09.005. Epub 2005 Oct 19.
Bilodeau S, Roussel-Gervais A, Drouin J. Distinct developmental roles of cell cycle inhibitors p57Kip2 and p27Kip1 distinguish pituitary progenitor cell cycle exit from cell cycle reentry of differentiated cells. Mol Cell Biol. 2009 Apr;29(7):1895-908. doi: 10.1128/MCB.01885-08. Epub 2009 Jan 12.
Tong Y, Tan Y, Zhou C, Melmed S. Pituitary tumor transforming gene interacts with Sp1 to modulate G1/S cell phase transition. Oncogene. 2007 Aug 16;26(38):5596-605. doi: 10.1038/sj.onc.1210339.
Park MS, Rosai J, Nguyen HT, Capodieci P, Cordon-Cardo C, Koff A. p27 and Rb are on overlapping pathways suppressing tumorigenesis in mice. Proc Natl Acad Sci U S A. 1999 May 25;96(11):6382-7. doi: 10.1073/pnas.96.11.6382.
Ramsey MR, Krishnamurthy J, Pei XH, Torrice C, Lin W, Carrasco DR, Ligon KL, Xiong Y, Sharpless NE. Expression of p16Ink4a compensates for p18Ink4c loss in cyclin-dependent kinase 4/6-dependent tumors and tissues. Cancer
Res. 2007 May 15;67(10):4732-41. doi: 10.1158/0008-5472.CAN-06-3437.
Roussel-Gervais A, Bilodeau S, Vallette S, et al. Cooperation between cyclin E and p27(Kip1) in pituitary tumorigenesis. Mol Endocrinol. 2010;24(9):1835‐1845. doi:10.1210/me.2010-0091.
Franklin DS, Godfrey VL, O'Brien DA, Deng C, Xiong Y. Functional collaboration between different cyclin-dependent kinase inhibitors suppresses tumor growth with distinct tissue specificity. Mol Cell Biol. 2000 Aug;20(16):6147-58. doi: 10.1128/mcb.20.16.6147-6158.2000.
Sotillo R, Renner O, Dubus P, Ruiz-Cabello J, Martín-Caballero J, Barbacid M, Carnero A, Malumbres M. Cooperation between Cdk4 and p27kip1 in tumor development: a preclinical model to evaluate cell cycle inhibitors with therapeutic activity. Cancer Res. 2005 May 1;65(9):3846-52. doi: 10.1158/0008-5472.CAN-04-4195.
Agarwal SK, Mateo CM, Marx SJ. Rare germline mutations in cyclin-dependent kinase inhibitor genes in multiple endocrine neoplasia type 1 and related states. J Clin Endocrinol Metab. 2009 May;94(5):1826-34. doi: 10.1210/jc.2008-2083. Epub 2009 Jan 13. Erratum in: J Clin Endocrinol Metab. 2009 Jul;94(7):2674.
Hernández-Ramírez LC, Gabrovska P, Dénes J, Stals K, Trivellin G, Tilley D, Ferrau F, Evanson J, Ellard S, Grossman AB, Roncaroli F, Gadelha MR, Korbonits M; International FIPA Consortium. Landscape of Familial Isolated and Young-Onset Pituitary Adenomas: Prospective Diagnosis in AIP Mutation Carriers. J Clin Endocrinol Metab. 2015 Sep;100(9):E1242-54. doi: 10.1210/jc.2015-1869.
Daly AF, Tichomirowa MA, Petrossians P, Heliövaara E, Jaffrain-Rea ML, Barlier A, Naves LA, Ebeling T, Karhu A, Raappana A, Cazabat L, De Menis E, Montañana CF, Raverot G, Weil RJ, Sane T, Maiter D, Neggers S, Yaneva M, Tabarin A, Verrua E, Eloranta E, Murat A, Vierimaa O, Salmela PI, Emy P, Toledo RA, Sabaté MI, Villa C, Popelier M, Salvatori R, Jennings J, Longás AF, LabartaAizpún JI, Georgitsi M, Paschke R, Ronchi C, Valimaki M, Saloranta C, De Herder W, Cozzi R, Guitelman M, Magri F, Lagonigro MS, Halaby G, Corman V, Hagelstein MT, Vanbellinghen JF, Barra GB, Gimenez-Roqueplo AP, Cameron FJ, Borson-Chazot F, Holdaway I, Toledo SP, Stalla GK, Spada A, Zacharieva S, Bertherat J, Brue T, Bours V, Chanson P, Aaltonen LA, Beckers A. Clinical characteristics and therapeutic responses in patients with germ-line AIP mutations and pituitary adenomas: an international collaborative study. J Clin Endocrinol Metab. 2010 Nov;95(11):E373-83. doi: 10.1210/jc.2009-2556
Oriola J, Lucas T, Halperin I, Mora M, Perales MJ, Alvarez-Escolá C, Paz de MN, Díaz Soto G, Salinas I, Julián MT, Olaizola I, Bernabeu I, Marazuela M, Puig-Domingo M. Germline mutations of AIP gene in somatotropinomas resistant to somatostatin analogues. Eur J Endocrinol. 2012 Dec 10;168(1):9-13. doi: 10.1530/EJE-12-0457.
Korbonits M, Storr H, Kumar AV. Familial pituitary adenomas - who should be tested for AIP mutations? Clin Endocrinol (Oxf). 2012 Sep;77(3):351-6. doi: 10.1111/j.1365-2265.2012.04445.x.
Beckers A, Lodish MB, Trivellin G, Rostomyan L, Lee M, Faucz FR, Yuan B, Choong CS, Caberg JH, Verrua E, Naves LA, Cheetham TD, Young J, Lysy PA, Petrossians P, Cotterill A, Shah NS, Metzger D, Castermans E, Ambrosio MR, Villa C, Strebkova N, Mazerkina N, Gaillard S, Barra GB, Casulari LA, Neggers SJ, Salvatori R, Jaffrain-Rea ML, Zacharin M, Santamaria BL, Zacharieva S, Lim EM, Mantovani G, Zatelli MC, Collins MT, Bonneville JF, Quezado M, Chittiboina P, Oldfield EH, Bours V, Liu P, W de Herder W, Pellegata N, Lupski JR, Daly AF, Stratakis CA. X-linked acrogigantism syndrome: clinical profile and therapeutic responses. EndocrRelat Cancer. 2015 Jun;22(3):353-67. doi: 10.1530/ERC-15-0038. Epub 2015 Feb 24.
Iacovazzo D, Caswell R, Bunce B, Jose S, Yuan B, Hernández-Ramírez LC, Kapur S, Caimari F, Evanson J, Ferraù F, Dang MN, Gabrovska P, Larkin SJ, Ansorge O, Rodd C, Vance ML, Ramírez-Renteria C, Mercado M, Goldstone AP, Buchfelder M, Burren CP, Gurlek A, Dutta P, Choong CS, Cheetham T, Trivellin G, Stratakis CA, Lopes MB, Grossman AB, Trouillas J, Lupski JR, Ellard S, Sampson JR, Roncaroli F, Korbonits M. Germline or somatic GPR101 duplication leads to X-linked acrogigantism: a clinico-pathological and genetic study. Acta NeuropatholCommun. 2016 Jun 1;4(1):56. doi: 10.1186/s40478-016-0328-1.
Hernández-Ramírez LC, Gam R, Valdés N, Lodish MB, Pankratz N, Balsalobre A, Gauthier Y, Faucz FR, Trivellin G, Chittiboina P, Lane J, Kay DM, Dimopoulos A, Gaillard S, Neou M, Bertherat J, Assié G, Villa C, Mills JL, Drouin J, Stratakis CA. Loss-of-function mutations in the CABLES1 gene are a novel cause of Cushing's disease. EndocrRelat Cancer. 2017 Aug;24(8):379-392. doi: 10.1530/ERC-17-0131.
Bernard V, Bouilly J, Beau I, Broutin I, Chanson P, Young J, Binart N. Germline Prolactin Receptor Mutation Is Not a Major Cause of Sporadic Prolactinoma in Humans. Neuroendocrinology. 2016;103(6):738-45. doi: 10.1159/000442981.
Melo FM, Couto PP, Bale AE, Bastos-Rodrigues L, Passos FM, Lisboa RG, Ng JM, Curran T, Dias EP, Friedman E, De Marco L. Whole-exome identifies RXRG and TH germline variants in familial isolated prolactinoma. Cancer Genet. 2016 Jun;209(6):251-7. doi: 10.1016/j.cancergen.2016.05.065.
Rostad S. Pituitary adenoma pathogenesis: anupdate. CurrOpinEndocrinol Diabetes Obes. 2012 Aug;19(4):322-7. doi: 10.1097/MED.0b013e328354b2e2.
Pellegata NS, Quintanilla-Martinez L, Siggelkow H, Samson E, Bink K, Höfler H, Fend F, Graw J, Atkinson MJ. Germ-line mutations in p27Kip1 cause a multiple endocrine neoplasia syndrome in rats and humans. Proc Natl Acad Sci U S A. 2006 Oct 17;103(42):15558-63. doi: 10.1073/pnas.0603877103. Epub 2006 Oct 9. Erratum in: Proc Natl Acad Sci U S A. 2006 Dec 12;103(50):19213.
Bertherat J, Horvath A, Groussin L, Grabar S, Boikos S, Cazabat L, Libe R, René-Corail F, Stergiopoulos S, Bourdeau I, Bei T, Clauser E, Calender A, Kirschner LS, Bertagna X, Carney JA, Stratakis CA. Mutations in regulatory subunit type 1A of cyclic adenosine 5'-monophosphate-dependent protein kinase (PRKAR1A): phenotype analysis in 353 patients and 80 different genotypes. J Clin Endocrinol Metab. 2009 Jun;94(6):2085-91. doi: 10.1210/jc.2008-2333.
de Kock L, Sabbaghian N, Plourde F, Srivastava A, Weber E, Bouron-Dal Soglio D, Hamel N, Choi JH, Park SH, Deal CL, Kelsey MM, Dishop MK, Esbenshade A, Kuttesch JF, Jacques TS, Perry A, Leichter H, Maeder P, Brundler MA, Warner J, Neal J, Zacharin M, Korbonits M, Cole T, Traunecker H, McLean TW, Rotondo F, Lepage P, Albrecht S, Horvath E, Kovacs K, Priest JR, Foulkes WD. Pituitary blastoma: a pathognomonic feature of germ-line DICER1 mutations. Acta Neuropathol. 2014 Jul;128(1):111-22. doi: 10.1007/s00401-014-1285-z.
Xekouki P, Szarek E, Bullova P, Giubellino A, Quezado M, Mastroyannis SA, Mastorakos P, Wassif CA, Raygada M, Rentia N, Dye L, Cougnoux A, Koziol D, Sierra Mde L, Lyssikatos C, Belyavskaya E, Malchoff C, Moline J, Eng C, Maher LJ 3rd, Pacak K, Lodish M, Stratakis CA. Pituitary adenoma with paraganglioma/pheochromocytoma (3PAs)
and succinate dehydrogenase defects in humans and mice. J Clin Endocrinol Metab. 2015 May;100(5):E710-9. doi: 10.1210/jc.2014-4297. Epub 2015 Feb 19.
Uraki S, Ariyasu H, Doi A, Furuta H, Nishi M, Sugano K, Inoshita N, Nakao N, Yamada S, Akamizu T. Atypical pituitary adenoma with MEN1 somatic mutation associated with abnormalities of DNA mismatch repair genes; MLH1 germline mutation and MSH6 somatic mutation. Endocr J. 2017 Sep 30;64(9):895-906. doi: 10.1507/endocrj.EJ17-0036.
Cohen M, Persky R, Stegemann R, Hernández-Ramírez LC, Zeltser D, Lodish MB, Chen A, Keil MF, Tatsi C, Faucz FR, Buchner DA, Stratakis CA, Tiosano D. Germline USP8 Mutation Associated With Pediatric Cushing Disease and Other Clinical Features: A New Syndrome. J Clin Endocrinol Metab. 2019 Oct 1;104(10):4676-4682. doi: 10.1210/jc.2019-00697.
Tigas S, Carroll PV, Jones R, Bingham E, Russell-Jones D, Powell M, Scobie IN. Simultaneous Cushing's disease and tuberous sclerosis; a potential role for TSC in pituitary ontogeny. Clin Endocrinol (Oxf). 2005 Dec;63(6):694-5. doi: 10.1111/j.1365-2265.2005.02374.x.
Välimäki N, Demir H, Pitkänen E, Kaasinen E, Karppinen A, Kivipelto L, Schalin-Jäntti C, Aaltonen LA, Karhu A. Whole-Genome Sequencing of Growth Hormone (GH)-Secreting Pituitary Adenomas. J Clin Endocrinol Metab. 2015 Oct;100(10):3918-27. doi: 10.1210/jc.2015-3129
Song ZJ, Reitman ZJ, Ma ZY, Chen JH, Zhang QL, Shou XF, Huang CX, Wang YF, Li SQ, Mao Y, Zhou LF, Lian BF, Yan H, Shi YY, Zhao Y. The genome-wide mutational landscape of pituitary adenomas. Cell Res. 2016 Nov;26(11):1255-1259. doi: 10.1038/cr.2016.114. Epub 2016 Sep 27.
Freda PU, Chung WK, Matsuoka N, Walsh JE, Kanibir MN, Kleinman G, Wang Y, Bruce JN, Post KD. Analysis of GNAS mutations in 60 growth hormone secreting pituitary tumors: correlation with clinical and pathological characteristics and surgical outcome based on highly sensitive GH and IGF-I criteria for remission. Pituitary. 2007;10(3):275-82. doi: 10.1007/s11102-007-0058-2.
Neou M, Villa C, Armignacco R, Jouinot A, Raffin-Sanson ML, Septier A, Letourneur F, Diry S, Diedisheim M, Izac B, Gaspar C, Perlemoine K, Verjus V, Bernier M, Boulin A, Emile JF, Bertagna X, Jaffrezic F, Laloe D, Baussart B, Bertherat J, Gaillard S, Assié G. Pangenomic Classification of Pituitary Neuroendocrine Tumors. Cancer Cell. 2020 Jan 13;37(1):123-134.e5. doi: 10.1016/j.ccell.2019.11.002.
Albright F, Butler AM, Hampton AO, Smith P. Syndrome Characterized by Osteitis Fibrosa Disseminata, Areas of Pigmentation and Endocrine Dysfunction, with Precocious Puberty in Females. N Engl J Med 1937; 216:727-746.
Reincke M, Sbiera S, Hayakawa A, Theodoropoulou M, Osswald A, Beuschlein F, Meitinger T, Mizuno-Yamasaki E, Kawaguchi K, Saeki Y, Tanaka K, Wieland T, Graf E, Saeger W, Ronchi CL, Allolio B, Buchfelder M, Strom TM, Fassnacht M, Komada M. Mutations in the deubiquitinase gene USP8 cause Cushing's disease. Nat Genet. 2015 Jan;47(1):31-8. doi: 10.1038/ng.3166.
Kurelac I, MacKay A, Lambros MB, Di Cesare E, Cenacchi G, Ceccarelli C, Morra I, Melcarne A, Morandi L, Calabrese FM, Attimonelli M, Tallini G, Reis-Filho JS, Gasparre G. Somatic complex I disruptive mitochondrial DNA mutations are modifiers of tumorigenesis that correlate with low genomic instability in pituitary adenomas. Hum Mol Genet. 2013 Jan 15;22(2):226-38. doi: 10.1093/hmg/dds422.
Bruns C, Lewis I, Briner U, Meno-Tetang G, Weckbecker G. SOM230: a novel somatostatin peptidomimetic with broad somatotropin release inhibiting factor (SRIF) receptor binding and a unique antisecretory profile. Eur J Endocrinol. 2002 May;146(5):707-16. doi: 10.1530/eje.0.1460707.
Perez-Rivas LG, Theodoropoulou M, Ferraù F, Nusser C, Kawaguchi K, Stratakis CA, Faucz FR, Wildemberg LE, Assié G, Beschorner R, Dimopoulou C, Buchfelder M, Popovic V, Berr CM, Tóth M, Ardisasmita AI, Honegger J, Bertherat J, Gadelha MR, Beuschlein F, Stalla G, Komada M, Korbonits M, Reincke M. The Gene of the Ubiquitin-Specific Protease 8 Is Frequently Mutated in Adenomas Causing Cushing's Disease. J Clin Endocrinol Metab. 2015 Jul;100(7):E997-1004. doi: 10.1210/jc.2015-1453. Epub 2015 May 5.
Losa M, Mortini P, Pagnano A, Detomas M, Cassarino MF, PecoriGiraldi F. Clinical characteristics and surgical outcome in USP8-mutated human adrenocorticotropic hormone-secreting pituitary adenomas. Endocrine. 2019 Feb;63(2):240-246. doi: 10.1007/s12020-018-1776-0.
Bengtsson D, Joost P, Aravidis C, AskmalmStenmark M, Backman AS, Melin B, von Salomé J, Zagoras T, Gebre-Medhin S, Burman P. Corticotroph Pituitary Carcinoma in a Patient With Lynch Syndrome (LS) and Pituitary Tumors in a Nationwide LS Cohort. J Clin Endocrinol Metab. 2017 Nov 1;102(11):3928-3932. doi: 10.1210/jc.2017-01401.
Tanizaki Y, Jin L, Scheithauer BW, Kovacs K, Roncaroli F, Lloyd RV. P53 gene mutations in pituitary carcinomas. EndocrPathol. 2007 Winter;18(4):217-22. doi: 10.1007/s12022-007-9006-y.
SrirangamNadhamuni V, Korbonits M. Novel insights into Pituitary Tumorigenesis: Genetic and Epigenetic Mechanisms. Endocr Rev. 2020 Mar 23:bnaa006. doi: 10.1210/endrev/bnaa006. Epub ahead of print.
Pease M, Ling C, Mack WJ, Wang K, Zada G. The role of epigenetic modification in tumorigenesis and progression of pituitary adenomas: a systematic review of the literature. PLoS One. 2013 Dec 18;8(12):e82619. doi: 10.1371/journal.pone.0082619. PMID: 24367530;
Dudley KJ, Revill K, Clayton RN, Farrell WE. Pituitary tumours: all silent on the epigenetics front. J Mol Endocrinol. 2009 Jun;42(6):461-8. doi: 10.1677/JME-09-0009
García-Martínez A, Sottile J, Sánchez-Tejada L, Fajardo C, Cámara R, Lamas C, Barberá VM, Picó A. DNA Methylation of Tumor Suppressor Genes in Pituitary Neuroendocrine Tumors. J Clin Endocrinol Metab. 2019 Apr 1;104(4):1272-1282. doi: 10.1210/jc.2018-01856.
Gadelha MR, Kasuki L, Dénes J, Trivellin G, Korbonits M.
MicroRNAs: Suggested role in pituitary adenoma
pathogenesis. J Endocrinol Invest. 2013 Nov;36(10):889-95.
doi: 10.1007/BF03346759.
Publicado
Cómo citar
Número
Sección
Licencia
Derechos de autor 2021 Universidad Nacional de Córdoba
Esta obra está bajo una licencia internacional Creative Commons Atribución-NoComercial 4.0.
La Revista de la Facultad de Ciencias Médicas de Córdoba (RFCM) adhiere a la política de Acceso Abierto y no cobra cargos a los autores para publicar, ni tampoco a lectores para acceder a los artículos publicados.
