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Pathology and pathogenesis of craniopharyngiomas

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Abstract

Craniopharyngiomas are benign but locally invasive tumours of the sellar region that occur as two subtypes. The adamantinomatous type (aCP) occurs mainly during childhood while the papillary type (pCP) is found almost exclusively in adults. It is thought that aCPs arise from ectopic embryonic remnants of Rathke’s pouch and these tumours share features with odontogenic tumours suggesting a common origin. The pathogenesis of pCPs is less understood but these tumours may arise from metaplastic transformation of anterior pituitary epithelial cells. Mutations in CTNNB1 that encodes β-catenin are found in around 70 % of aCPs. These mutations stabilise β-catenin, which evades destruction and accumulates in the nucleus and cytosol leading to constitutive activation of the Wnt signaling pathway. Expression of mutant β-catenin early in mouse pituitary development promotes the formation of tumours similar to aCPs. However, accumulation of β-catenin occurs only in small clusters of tumour cells even though the mutation is ubiquitous. These cell clusters are slow-growing and share some characteristics with pituitary stem cells. They are often present at the invading edge and express growth factors that may participate in paracrine signaling to surrounding cells. β-Catenin nuclear translocation may also occur in the absence of CTNNB1 mutations, suggesting that other genetic or epigenetic events can activate Wnt signaling in aCP. These mechanisms, as well as those underlying the molecular pathogenesis of pCPs remain to be identified.

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References

  1. Bunin GR, Surawicz TS, Witman PA, Preston-Martin S, Davis F, Bruner JM (1998) The descriptive epidemiology of craniopharyngioma. J Neurosurg 89(4):547–551. doi:10.3171/jns.1998.89.4.0547

    Article  PubMed  CAS  Google Scholar 

  2. Crotty TB, Scheithauer BW, Young WF Jr, Davis DH, Shaw EG, Miller GM, Burger PC (1995) Papillary craniopharyngioma: a clinicopathological study of 48 cases. J Neurosurg 83(2):206–214. doi:10.3171/jns.1995.83.2.0206

    Article  PubMed  CAS  Google Scholar 

  3. Hofmann BM, Kreutzer J, Saeger W, Buchfelder M, Blumcke I, Fahlbusch R, Buslei R (2006) Nuclear β-catenin accumulation as reliable marker for the differentiation between cystic craniopharyngiomas and rathke cleft cysts: a clinico-pathologic approach. Am J Surg Pathol 30(12):1595–1603. doi:10.1097/01.pas.0000213328.64121.12

    Article  PubMed  Google Scholar 

  4. Shin JL, Asa SL, Woodhouse LJ, Smyth HS, Ezzat S (1999) Cystic lesions of the pituitary: clinicopathological features distinguishing craniopharyngioma, Rathke’s cleft cyst, and arachnoid cyst. J Clin Endocrinol Metab 84(11):3972–3982

    Article  PubMed  CAS  Google Scholar 

  5. Okada T, Fujitsu K, Ichikawa T, Mukaihara S, Miyahara K, Kaku S, Uryuu Y, Niino H, Yagishita S, Shiina T (2011) Coexistence of adamantinomatous and squamous-papillary type craniopharyngioma: case report and discussion of etiology and pathology. Neuropathology. doi:10.1111/j.1440-1789.2011.01235.x

    PubMed  Google Scholar 

  6. Sekine S, Takata T, Shibata T, Mori M, Morishita Y, Noguchi M, Uchida T, Kanai Y, Hirohashi S (2004) Expression of enamel proteins and LEF1 in adamantinomatous craniopharyngioma: evidence for its odontogenic epithelial differentiation. Histopathology 45(6):573–579. doi:10.1111/j.1365-2559.2004.02029.x

    Article  PubMed  CAS  Google Scholar 

  7. Harrison MJ, Morgello S, Post KD (1994) Epithelial cystic lesions of the sellar and parasellar region: a continuum of ectodermal derivatives? J Neurosurg 80(6):1018–1025. doi:10.3171/jns.1994.80.6.1018

    Article  PubMed  CAS  Google Scholar 

  8. Oka H, Kawano N, Yagishita S, Kobayashi I, Saegusa H, Fujii K (1997) Ciliated craniopharyngioma indicates histogenetic relationship to Rathke cleft epithelium. Clin Neuropathol 16(2):103–106

    PubMed  CAS  Google Scholar 

  9. Goodrich JT, Post KD, Duffy P (1985) Ciliated craniopharyngioma. Surg Neurol 24(1):105–111

    Article  PubMed  CAS  Google Scholar 

  10. Karavitaki N, Wass JA (2009) Non-adenomatous pituitary tumours. Best Pract Res Clin Endocrinol Metab 23(5):651–665. doi:10.1016/j.beem.2009.05.007

    Article  PubMed  CAS  Google Scholar 

  11. Prabhu VC, Brown HG (2005) The pathogenesis of craniopharyngiomas. Childs Nerv Syst 21(8–9):622–627. doi:10.1007/s00381-005-1190-9

    Article  PubMed  Google Scholar 

  12. Zhu X, Gleiberman AS, Rosenfeld MG (2007) Molecular physiology of pituitary development: signaling and transcriptional networks. Physiol Rev 87(3):933–963. doi:10.1152/physrev.00006.2006

    Article  PubMed  CAS  Google Scholar 

  13. Olson LE, Tollkuhn J, Scafoglio C, Krones A, Zhang J, Ohgi KA, Wu W, Taketo MM, Kemler R, Grosschedl R, Rose D, Li X, Rosenfeld MG (2006) Homeodomain-mediated β-catenin-dependent switching events dictate cell-lineage determination. Cell 125(3):593–605. doi:10.1016/j.cell.2006.02.046

    Article  PubMed  CAS  Google Scholar 

  14. Liu C, Li Y, Semenov M, Han C, Baeg GH, Tan Y, Zhang Z, Lin X, He X (2002) Control of β-catenin phosphorylation/degradation by a dual-kinase mechanism. Cell 108(6):837–847

    Article  PubMed  CAS  Google Scholar 

  15. Kitagawa M, Hatakeyama S, Shirane M, Matsumoto M, Ishida N, Hattori K, Nakamichi I, Kikuchi A, Nakayama K (1999) An F-box protein, FWD1, mediates ubiquitin-dependent proteolysis of β-catenin. EMBO J 18(9):2401–2410. doi:10.1093/emboj/18.9.2401

    Article  PubMed  CAS  Google Scholar 

  16. Hart M, Concordet JP, Lassot I, Albert I, del los Santos R, Durand H, Perret V, Rubinfeld B, Margottin F, Benarous R, Polakis P (1999) The F-box protein β-TrCP associates with phosphorylated β-catenin and regulates its activity in the cell. Curr Biol 9(4):207–210

    Article  PubMed  CAS  Google Scholar 

  17. Bhanot P, Brink M, Samos CH, Hsieh JC, Wang Y, Macke JP, Andrew D, Nathans J, Nusse R (1996) A new member of the frizzled family from Drosophila functions as a Wingless receptor. Nature 382(6588):225–230. doi:10.1038/382225a0

    Article  PubMed  CAS  Google Scholar 

  18. Wu CH, Nusse R (2002) Ligand receptor interactions in the Wnt signaling pathway in Drosophila. J Biol Chem 277(44):41762–41769. doi:10.1074/jbc.M207850200

    Article  PubMed  CAS  Google Scholar 

  19. Mao J, Wang J, Liu B, Pan W, Farr GH 3rd, Flynn C, Yuan H, Takada S, Kimelman D, Li L, Wu D (2001) Low-density lipoprotein receptor-related protein-5 binds to Axin and regulates the canonical Wnt signaling pathway. Mol Cell 7(4):801–809

    Article  PubMed  CAS  Google Scholar 

  20. Davidson G, Wu W, Shen J, Bilic J, Fenger U, Stannek P, Glinka A, Niehrs C (2005) Casein kinase 1 gamma couples Wnt receptor activation to cytoplasmic signal transduction. Nature 438(7069):867–872. doi:10.1038/nature04170

    Article  PubMed  CAS  Google Scholar 

  21. Zeng X, Tamai K, Doble B, Li S, Huang H, Habas R, Okamura H, Woodgett J, He X (2005) A dual-kinase mechanism for Wnt co-receptor phosphorylation and activation. Nature 438(7069):873–877. doi:10.1038/nature04185

    Article  PubMed  CAS  Google Scholar 

  22. Behrens J, von Kries JP, Kuhl M, Bruhn L, Wedlich D, Grosschedl R, Birchmeier W (1996) Functional interaction of β-catenin with the transcription factor LEF-1. Nature 382(6592):638–642. doi:10.1038/382638a0

    Article  PubMed  CAS  Google Scholar 

  23. Cavallo RA, Cox RT, Moline MM, Roose J, Polevoy GA, Clevers H, Peifer M, Bejsovec A (1998) Drosophila Tcf and Groucho interact to repress Wingless signalling activity. Nature 395(6702):604–608. doi:10.1038/26982

    Article  PubMed  CAS  Google Scholar 

  24. Korswagen HC, Herman MA, Clevers HC (2000) Distinct β-catenins mediate adhesion and signalling functions in C. elegans. Nature 406(6795):527–532. doi:10.1038/35020099

    Article  PubMed  CAS  Google Scholar 

  25. von Kries JP, Winbeck G, Asbrand C, Schwarz-Romond T, Sochnikova N, Dell’Oro A, Behrens J, Birchmeier W (2000) Hot spots in β-catenin for interactions with LEF-1, conductin and APC. Nat Struct Biol 7(9):800–807. doi:10.1038/79039

    Article  Google Scholar 

  26. Gottardi CJ, Gumbiner BM (2004) Distinct molecular forms of β-catenin are targeted to adhesive or transcriptional complexes. J Cell Biol 167(2):339–349. doi:10.1083/jcb.200402153

    Article  PubMed  CAS  Google Scholar 

  27. Buslei R, Nolde M, Hofmann B, Meissner S, Eyupoglu IY, Siebzehnrubl F, Hahnen E, Kreutzer J, Fahlbusch R (2005) Common mutations of β-catenin in adamantinomatous craniopharyngiomas but not in other tumours originating from the sellar region. Acta Neuropathol 109(6):589–597. doi:10.1007/s00401-005-1004-x

    Article  PubMed  CAS  Google Scholar 

  28. Sekine S, Shibata T, Kokubu A, Morishita Y, Noguchi M, Nakanishi Y, Sakamoto M, Hirohashi S (2002) Craniopharyngiomas of adamantinomatous type harbor β-catenin gene mutations. Am J Pathol 161(6):1997–2001

    Article  PubMed  CAS  Google Scholar 

  29. Oikonomou E, Barreto DC, Soares B, De Marco L, Buchfelder M, Adams EF (2005) β-catenin mutations in craniopharyngiomas and pituitary adenomas. J Neurooncol 73(3):205–209. doi:10.1007/s11060-004-5232-z

    Article  PubMed  CAS  Google Scholar 

  30. Andoniadou CL, Gaston-Massuet C, Reddy R, Schneider RP, Blasco MA, Le Tissier P, Jacques TS, Pevny LH, Dattani MT, Martinez-Barbera JP (2012) Identification of novel pathways involved in the pathogenesis of human adamantinomatous craniopharyngioma. Acta Neuropathol. doi:10.1007/s00401-012-0957-9

    PubMed  Google Scholar 

  31. Hassanein AM, Glanz SM, Kessler HP, Eskin TA, Liu C (2003) β-Catenin is expressed aberrantly in tumors expressing shadow cells. Pilomatricoma, craniopharyngioma, and calcifying odontogenic cyst. Am J Clin Pathol 120(5):732–736. doi:10.1309/EALE-G7LD-6W71-67PX

    Google Scholar 

  32. Holsken A, Kreutzer J, Hofmann BM, Hans V, Oppel F, Buchfelder M, Fahlbusch R, Blumcke I, Buslei R (2009) Target gene activation of the Wnt signaling pathway in nuclear β-catenin accumulating cells of adamantinomatous craniopharyngiomas. Brain Pathol 19(3):357–364. doi:10.1111/j.1750-3639.2008.00180.x

    Article  PubMed  Google Scholar 

  33. Paulus W, Stockel C, Krauss J, Sorensen N, Roggendorf W (1997) Odontogenic classification of craniopharyngiomas: a clinicopathological study of 54 cases. Histopathology 30(2):172–176

    Article  PubMed  CAS  Google Scholar 

  34. Ahn SG, Kim SA, Kim SG, Lee SH, Kim J, Yoon JH (2008) β-catenin gene alterations in a variety of so-called calcifying odontogenic cysts. APMIS 116(3):206–211. doi:10.1111/j.1600-0463.2008.00893.x

    Article  PubMed  CAS  Google Scholar 

  35. Sekine S, Sato S, Takata T, Fukuda Y, Ishida T, Kishino M, Shibata T, Kanai Y, Hirohashi S (2003) β-catenin mutations are frequent in calcifying odontogenic cysts, but rare in ameloblastomas. Am J Pathol 163(5):1707–1712

    Article  PubMed  CAS  Google Scholar 

  36. VanGilder JC, Inukai J (1973) Growth characteristics of experimental intracerebrally transplanted oral epithelium. J Neurosurg 38(5):608–615. doi:10.3171/jns.1973.38.5.0608

    Article  PubMed  CAS  Google Scholar 

  37. Gaston-Massuet C, Andoniadou CL, Signore M, Jayakody SA, Charolidi N, Kyeyune R, Vernay B, Jacques TS, Taketo MM, Le Tissier P, Dattani MT, Martinez-Barbera JP (2011) Increased Wingless (Wnt) signaling in pituitary progenitor/stem cells gives rise to pituitary tumors in mice and humans. Proc Natl Acad Sci USA 108(28):11482–11487. doi:10.1073/pnas.1101553108

    Article  PubMed  CAS  Google Scholar 

  38. Gaston-Massuet C, Andoniadou CL, Signore M, Sajedi E, Bird S, Turner JM, Martinez-Barbera JP (2008) Genetic interaction between the homeobox transcription factors HESX1 and SIX3 is required for normal pituitary development. Dev Biol 324(2):322–333. doi:10.1016/j.ydbio.2008.08.008

    Article  PubMed  CAS  Google Scholar 

  39. Thomas P, Beddington R (1996) Anterior primitive endoderm may be responsible for patterning the anterior neural plate in the mouse embryo. Curr Biol 6(11):1487–1496

    Article  PubMed  CAS  Google Scholar 

  40. Chu PG, Weiss LM (2002) Keratin expression in human tissues and neoplasms. Histopathology 40(5):403–439

    Article  PubMed  CAS  Google Scholar 

  41. Bunin GR, Surawicz TS, Witman PA, Preston-Martin S, Davis F, Bruner JM (1998) The descriptive epidemiology of craniopharyngioma. J Neurosurg 89(4):547–551. doi:10.3171/jns.1998.89.4.0547

    Article  PubMed  CAS  Google Scholar 

  42. Garcia-Lavandeira M, Saez C, Diaz-Rodriguez E, Perez-Romero S, Senra A, Dieguez C, Japon MA, Alvarez CV (2012) Craniopharyngiomas express embryonic stem cell markers (SOX2, OCT4, KLF4, and SOX9) as pituitary stem cells but do not coexpress RET/GFRA3 receptors. J Clin Endocrinol Metab 97(1):E80–E87. doi:10.1210/jc.2011-2187

    Article  PubMed  CAS  Google Scholar 

  43. Fauquier T, Rizzoti K, Dattani M, Lovell-Badge R, Robinson IC (2008) SOX2-expressing progenitor cells generate all of the major cell types in the adult mouse pituitary gland. Proc Natl Acad Sci USA 105(8):2907–2912. doi:10.1073/pnas.0707886105

    Article  PubMed  CAS  Google Scholar 

  44. Gleiberman AS, Michurina T, Encinas JM, Roig JL, Krasnov P, Balordi F, Fishell G, Rosenfeld MG, Enikolopov G (2008) Genetic approaches identify adult pituitary stem cells. Proc Natl Acad Sci USA 105(17):6332–6337. doi:10.1073/pnas.0801644105

    Article  PubMed  CAS  Google Scholar 

  45. Treier M, O’Connell S, Gleiberman A, Price J, Szeto DP, Burgess R, Chuang PT, McMahon AP, Rosenfeld MG (2001) Hedgehog signaling is required for pituitary gland development. Development 128(3):377–386

    PubMed  CAS  Google Scholar 

  46. Wang Y, Martin JF, Bai CB (2010) Direct and indirect requirements of Shh/Gli signaling in early pituitary development. Dev Biol 348(2):199–209. doi:10.1016/j.ydbio.2010.09.024

    Article  PubMed  CAS  Google Scholar 

  47. Hutchin ME, Kariapper MS, Grachtchouk M, Wang A, Wei L, Cummings D, Liu J, Michael LE, Glick A, Dlugosz AA (2005) Sustained Hedgehog signaling is required for basal cell carcinoma proliferation and survival: conditional skin tumorigenesis recapitulates the hair growth cycle. Genes Dev 19(2):214–223. doi:10.1101/gad.1258705

    Article  PubMed  CAS  Google Scholar 

  48. Mao L, Xia YP, Zhou YN, Dai RL, Yang X, Duan SJ, Qiao X, Mei YW, Hu B, Cui H (2009) A critical role of Sonic Hedgehog signaling in maintaining the tumorigenicity of neuroblastoma cells. Cancer Sci 100(10):1848–1855. doi:10.1111/j.1349-7006.2009.01262.x

    Article  PubMed  CAS  Google Scholar 

  49. Park KS, Martelotto LG, Peifer M, Sos ML, Karnezis AN, Mahjoub MR, Bernard K, Conklin JF, Szczepny A, Yuan J, Guo R, Ospina B, Falzon J, Bennett S, Brown TJ, Markovic A, Devereux WL, Ocasio CA, Chen JK, Stearns T, Thomas RK, Dorsch M, Buonamici S, Watkins DN, Peacock CD, Sage J (2011) A crucial requirement for Hedgehog signaling in small cell lung cancer. Nat Med 17(11):1504–1508. doi:10.1038/nm.2473

    Article  PubMed  CAS  Google Scholar 

  50. Yoo YA, Kang MH, Lee HJ, Kim BH, Park JK, Kim HK, Kim JS, Oh SC (2011) Sonic Hedgehog pathway promotes metastasis and lymphangiogenesis via activation of Akt, EMT, and MMP-9 pathway in gastric cancer. Cancer Res 71(22):7061–7070. doi:10.1158/0008-5472.CAN-11-1338

    Article  PubMed  CAS  Google Scholar 

  51. Ericson J, Norlin S, Jessell TM, Edlund T (1998) Integrated FGF and BMP signaling controls the progression of progenitor cell differentiation and the emergence of pattern in the embryonic anterior pituitary. Development 125(6):1005–1015

    PubMed  CAS  Google Scholar 

  52. Wesche J, Haglund K, Haugsten EM (2011) Fibroblast growth factors and their receptors in cancer. Biochem J 437(2):199–213. doi:10.1042/BJ20101603

    Article  PubMed  CAS  Google Scholar 

  53. Holsken A, Buchfelder M, Fahlbusch R, Blumcke I, Buslei R (2010) Tumour cell migration in adamantinomatous craniopharyngiomas is promoted by activated Wnt-signalling. Acta Neuropathol 119(5):631–639. doi:10.1007/s00401-010-0642-9

    Article  PubMed  Google Scholar 

  54. Yamashiro S, Yamakita Y, Ono S, Matsumura F (1998) Fascin, an actin-bundling protein, induces membrane protrusions and increases cell motility of epithelial cells. Mol Biol Cell 9(5):993–1006

    PubMed  CAS  Google Scholar 

  55. Sartoretti-Schefer S, Wichmann W, Aguzzi A, Valavanis A (1997) MR differentiation of adamantinous and squamous-papillary craniopharyngiomas. AJNR Am J Neuroradiol 18(1):77–87

    PubMed  CAS  Google Scholar 

  56. Holsken A, Gebhardt M, Buchfelder M, Fahlbusch R, Blumcke I, Buslei R (2011) EGFR signaling regulates tumor cell migration in craniopharyngiomas. Clin Cancer Res 17(13):4367–4377. doi:10.1158/1078-0432.CCR-10-2811

    Article  PubMed  Google Scholar 

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Acknowledgments

The authors gratefully acknowledge support by the NIHR Oxford Biomedical Research Centre.

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The authors declare that they have no conflict of interest.

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  1. Nuffield Department of Clinical Neurosciences, Headley Way, Oxford, OX3 9DU, UK

    Sarah J. Larkin & Olaf Ansorge

  2. Department of Neuropathology, John Radcliffe Hospital, Headley Way, Oxford, OX3 9DU, UK

    Sarah J. Larkin & Olaf Ansorge

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Larkin, S.J., Ansorge, O. Pathology and pathogenesis of craniopharyngiomas. Pituitary 16, 9–17 (2013). https://doi.org/10.1007/s11102-012-0418-4

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