Skip to main content
SpringerLink
Log in

Molecular Targets in Craniopharyngioma

  • Chapter
  • First Online:
Book cover Adult Craniopharyngiomas

Abstract

Craniopharyngiomas have been histologically categorized into adamantinomatous (ACP) and papillary (PCP) subtype of craniopharyngioma. However, recent developments in molecular and genetic analysis have identified specific mutations in each, β-catenin in ACP and BRAF mutation in PCP. Furthermore, these developments have provided a deeper insight into the origin and pathology of this tumour and opened a new field of treatment opportunities. Recent findings indicate connection between stem cells and ACP and suggest a paracrine model in which pituitary stem cells drive neoplastic proliferation of nearby epithelial cells through growth factor signalling. Investigation of molecular and genetic alterations in CPs has identified several biomarkers that have paved the way for new possibility to predict the biological behaviour of this tumour as well as early diagnosis of recurrence and new treatment options. Currently, the most promising adjuvant treatment is offered by dual therapy with BRAF and MEK inhibitors in PCPs expressing BRAFV600E mutation. So far this has been reported as case studies, hence, ongoing and upcoming larger clinical trials are highly anticipated to provide more information on this treatment option and its long-term efficacy.

It might be possible that in the future, emerging treatments may be applied to reduce the tumour size and facilitate total surgical removal of the tumours potentially improving the outcome. Or even more exciting, simple analysis of tumour markers in serum and/or cerebrospinal fluid in combination with MR imaging would provide sufficient information on diagnosis and available targeted therapy could be applied precluding any surgical intervention.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 54.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Cushing H. Intracranial tumors. Notes upon series of two thousand verified cases with surgical mortality percentages pertaining thereto. Springfield, IL: Thomas; 1932.

    Google Scholar 

  2. Bulow B, Attewell R, Hagmar L, Malmstrom P, Nordstrom CH, Erfurth EM. Postoperative prognosis in craniopharyngioma with respect to cardiovascular mortality, survival, and tumor recurrence. J Clin Endocrinol Metab. 1998;83:3897–904.

    CAS  PubMed  Google Scholar 

  3. Brastianos PK, Taylor-Weiner A, Manley PE, et al. Exome sequencing identifies BRAF mutations in papillary craniopharyngiomas. Nat Genet. 2014;46:161–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Goschzik T, Gessi M, Dreschmann V, et al. Genomic alterations of adamantinomatous and papillary craniopharyngioma. J Neuropathol Exp Neurol. 2017;76:126–34.

    CAS  PubMed  Google Scholar 

  5. Holsken A, Sill M, Merkle J, et al. Adamantinomatous and papillary craniopharyngiomas are characterized by distinct epigenomic as well as mutational and transcriptomic profiles. Acta Neuropathol Commun. 2016;4:20.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Martinez-Gutierrez JC, D’Andrea MR, Cahill DP, Santagata S, Barker FG 2nd, Brastianos PK. Diagnosis and management of craniopharyngiomas in the era of genomics and targeted therapy. Neurosurg Focus. 2016;41:E2.

    Article  PubMed  Google Scholar 

  7. Gaston-Massuet C, Andoniadou CL, Signore M, et al. Increased wingless (Wnt) signaling in pituitary progenitor/stem cells gives rise to pituitary tumors in mice and humans. Proc Natl Acad Sci U S A. 2011;108:11482–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Martinez-Barbera JP. 60 Years of neuroendocrinology: biology of human craniopharyngioma: lessons from mouse models. J Endocrinol. 2015;226:T161–72.

    Article  CAS  PubMed  Google Scholar 

  9. Sekine S, Shibata T, Kokubu A, et al. Craniopharyngiomas of adamantinomatous type harbor beta-catenin gene mutations. Am J Pathol. 2002;161:1997–2001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Logan CY, Nusse R. The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol. 2004;20:781–810.

    Article  CAS  PubMed  Google Scholar 

  11. Polakis P. The many ways of Wnt in cancer. Curr Opin Genet Dev. 2007;17:45–51.

    Article  CAS  PubMed  Google Scholar 

  12. Hofmann BM, Kreutzer J, Saeger W, et al. Nuclear beta-catenin accumulation as reliable marker for the differentiation between cystic craniopharyngiomas and Rathke cleft cysts: a clinico-pathologic approach. Am J Surg Pathol. 2006;30:1595–603.

    Article  PubMed  Google Scholar 

  13. Juca CEB, Colli LM, Martins CS, et al. Impact of the canonical Wnt pathway activation on the pathogenesis and prognosis of adamantinomatous craniopharyngiomas. Horm Metab Res. 2018;50:575–81.

    Article  CAS  PubMed  Google Scholar 

  14. Voronkov A, Krauss S. Wnt/beta-catenin signaling and small molecule inhibitors. Curr Pharm Des. 2013;19:634–64.

    Article  CAS  PubMed  Google Scholar 

  15. Holsken A, Gebhardt M, Buchfelder M, Fahlbusch R, Blumcke I, Buslei R. EGFR signaling regulates tumor cell migration in craniopharyngiomas. Clin Cancer Res. 2011;17:4367–77.

    Article  PubMed  CAS  Google Scholar 

  16. Olsen JJ, Pohl SO, Deshmukh A, et al. The role of Wnt signalling in angiogenesis. Clin Biochem Rev. 2017;38:131–42.

    PubMed  PubMed Central  Google Scholar 

  17. Davies H, Bignell GR, Cox C, et al. Mutations of the BRAF gene in human cancer. Nature. 2002;417:949–54.

    Article  CAS  PubMed  Google Scholar 

  18. La Corte E, Younus I, Pivari F, et al. BRAF V600E mutant papillary craniopharyngiomas: a single-institutional case series. Pituitary. 2018;21:571–83.

    Article  PubMed  Google Scholar 

  19. Sperveslage J, Gierke M, Capper D, et al. VE1 immunohistochemistry in pituitary adenomas is not associated with BRAF V600E mutation. Acta Neuropathol. 2013;125:911–2.

    Article  PubMed  Google Scholar 

  20. Mordes DA, Lynch K, Campbell S, et al. VE1 antibody immunoreactivity in normal anterior pituitary and adrenal cortex without detectable BRAF V600E mutations. Am J Clin Pathol. 2014;141:811–5.

    Article  PubMed  Google Scholar 

  21. Weiner HL, Wisoff JH, Rosenberg ME, et al. Craniopharyngiomas: a clinicopathological analysis of factors predictive of recurrence and functional outcome. Neurosurgery. 1994;35:1001–10; discussion 10–11.

    Article  CAS  PubMed  Google Scholar 

  22. Larkin SJ, Preda V, Karavitaki N, Grossman A, Ansorge O. BRAF V600E mutations are characteristic for papillary craniopharyngioma and may coexist with CTNNB1-mutated adamantinomatous craniopharyngioma. Acta Neuropathol. 2014;127:927–9.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Crotty TB, Scheithauer BW, Young WF Jr, et al. Papillary craniopharyngioma: a clinicopathological study of 48 cases. J Neurosurg. 1995;83:206–14.

    Article  CAS  PubMed  Google Scholar 

  24. Szeifert GT, Sipos L, Horvath M, et al. Pathological characteristics of surgically removed craniopharyngiomas: analysis of 131 cases. Acta Neurochir. 1993;124:139–43.

    Article  CAS  PubMed  Google Scholar 

  25. Okada T, Fujitsu K, Ichikawa T, et al. Coexistence of adamantinomatous and squamous-papillary type craniopharyngioma: case report and discussion of etiology and pathology. Neuropathology. 2012;32:171–3.

    Article  PubMed  Google Scholar 

  26. Miller DC. Pathology of craniopharyngiomas: clinical import of pathological findings. Pediatr Neurosurg. 1994;21(Suppl 1):11–7.

    Article  PubMed  Google Scholar 

  27. Bi WL, Greenwald NF, Ramkissoon SH, et al. Clinical identification of oncogenic drivers and copy-number alterations in pituitary tumors. Endocrinology. 2017;158:2284–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Yamada H, Haratake J, Narasaki T, Oda T. Embryonal craniopharyngioma. Case report of the morphogenesis of a craniopharyngioma. Cancer. 1995;75:2971–7.

    Article  CAS  PubMed  Google Scholar 

  29. Garcia-Lavandeira M, Quereda V, Flores I, et al. A GRFa2/Prop1/stem (GPS) cell niche in the pituitary. PLoS One. 2009;4:e4815.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. Garcia-Lavandeira M, Saez C, Diaz-Rodriguez E, et al. 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. 2012;97:E80–7.

    Article  CAS  PubMed  Google Scholar 

  31. Holsken A, Stache C, Schlaffer SM, et al. Adamantinomatous craniopharyngiomas express tumor stem cell markers in cells with activated Wnt signaling: further evidence for the existence of a tumor stem cell niche? Pituitary. 2014;17:546–56.

    Article  PubMed  CAS  Google Scholar 

  32. Chang CV, Araujo RV, Cirqueira CS, et al. Differential expression of stem cell markers in human adamantinomatous craniopharyngioma and pituitary adenoma. Neuroendocrinology. 2017;104:183–93.

    Article  CAS  PubMed  Google Scholar 

  33. Haston S, Pozzi S, Carreno G, et al. MAPK pathway control of stem cell proliferation and differentiation in the embryonic pituitary provides insights into the pathogenesis of papillary craniopharyngioma. Development. 2017;144:2141–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Samis J, Vanin EF, Sredni ST, et al. Extensive miRNA expression analysis in craniopharyngiomas. Childs Nerv Syst. 2016;32:1617–24.

    Article  PubMed  Google Scholar 

  35. Campanini ML, Colli LM, Paixao BM, et al. CTNNB1 gene mutations, pituitary transcription factors, and MicroRNA expression involvement in the pathogenesis of adamantinomatous craniopharyngiomas. Horm Cancer. 2010;1:187–96.

    Article  CAS  PubMed  Google Scholar 

  36. Tena-Suck ML, Salinas-Lara C, Arce-Arellano RI, et al. Clinico-pathological and immunohistochemical characteristics associated to recurrence/regrowth of craniopharyngiomas. Clin Neurol Neurosurg. 2006;108:661–9.

    Article  PubMed  Google Scholar 

  37. Nishi T, Kuratsu J, Takeshima H, Saito Y, Kochi M, Ushio Y. Prognostic significance of the MIB-1 labeling index for patient with craniopharyngioma. Int J Mol Med. 1999;3:157–61.

    CAS  PubMed  Google Scholar 

  38. Prieto R, Pascual JM, Subhi-Issa I, Jorquera M, Yus M, Martinez R. Predictive factors for craniopharyngioma recurrence: a systematic review and illustrative case report of a rapid recurrence. World Neurosurg. 2013;79:733–49.

    Article  PubMed  Google Scholar 

  39. Xia Z, Liu W, Li S, et al. Expression of matrix metalloproteinase-9, type IV collagen and vascular endothelial growth factor in adamantinous craniopharyngioma. Neurochem Res. 2011;36:2346–51.

    Article  CAS  PubMed  Google Scholar 

  40. Gomes DC, Jamra SA, Leal LF, et al. Sonic hedgehog pathway is upregulated in adamantinomatous craniopharyngiomas. Eur J Endocrinol. 2015;172:603–8.

    Article  CAS  PubMed  Google Scholar 

  41. Lefranc F, Mijatovic T, Decaestecker C, et al. Monitoring the expression profiles of integrins and adhesion/growth-regulatory galectins in adamantinomatous craniopharyngiomas: their ability to regulate tumor adhesiveness to surrounding tissue and their contribution to prognosis. Neurosurgery. 2005;56:763–76.

    Article  PubMed  Google Scholar 

  42. Lubansu A, Ruchoux MM, Brotchi J, Salmon I, Kiss R, Lefranc F. Cathepsin B, D and K expression in adamantinomatous craniopharyngiomas relates to their levels of differentiation as determined by the patterns of retinoic acid receptor expression. Histopathology. 2003;43:563–72.

    Article  CAS  PubMed  Google Scholar 

  43. Guadagno E, de Divitiis O, Solari D, et al. Can recurrences be predicted in craniopharyngiomas? Beta-catenin coexisting with stem cells markers and p-ATM in a clinicopathologic study of 45cases. J Exp Clin Cancer Res. 2017;36:95.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Gong J, Zhang H, Xing S, et al. High expression levels of CXCL12 and CXCR4 predict recurrence of adamanti-nomatous craniopharyngiomas in children. Cancer Biomark. 2014;14:241–51.

    Article  PubMed  CAS  Google Scholar 

  45. Yin X, Liu Z, Zhu P, et al. CXCL12/CXCR4 promotes proliferation, migration, and invasion of adamantinomatous craniopharyngiomas via PI3K/AKT signal pathway. J Cell Biochem. 2019;120(6):9724–36. https://doi.org/10.1002/jcb.28253. Epub 2018 Dec 23.

  46. Vidal S, Kovacs K, Lloyd RV, Meyer FB, Scheithauer BW. Angiogenesis in patients with craniopharyngiomas: correlation with treatment and outcome. Cancer. 2002;94:738–45.

    Article  PubMed  Google Scholar 

  47. Xu J, You C, Zhang S, et al. Angiogenesis and cell proliferation in human craniopharyngioma xenografts in nude mice. J Neurosurg. 2006;105:306–10.

    Article  PubMed  Google Scholar 

  48. Donson AM, Apps J, Griesinger AM, et al. Molecular analyses reveal inflammatory mediators in the solid component and cyst fluid of human adamantinomatous craniopharyngioma. J Neuropathol Exp Neurol. 2017;76:779–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Satoh H, Uozumi T, Arita K, et al. Spontaneous rupture of craniopharyngioma cysts. A report of five cases and review of the literature. Surg Neurol. 1993;40:414–9.

    Article  CAS  PubMed  Google Scholar 

  50. Mori M, Takeshima H, Kuratsu J. Expression of interleukin-6 in human craniopharyngiomas: a possible inducer of tumor-associated inflammation. Int J Mol Med. 2004;14:505–9.

    CAS  PubMed  Google Scholar 

  51. Bartels U, Laperriere N, Bouffet E, Drake J. Intracystic therapies for cystic craniopharyngioma in childhood. Front Endocrinol (Lausanne). 2012;3:39.

    Article  Google Scholar 

  52. Chen M, Zheng SH, Yang M, Chen ZH, Li ST. The diagnostic value of preoperative inflammatory markers in craniopharyngioma: a multicenter cohort study. J Neuro-Oncol. 2018;138:113–22.

    Article  CAS  Google Scholar 

  53. Coy S, Rashid R, Lin JR, et al. Multiplexed immunofluorescence reveals potential PD-1/PD-L1 pathway vulnerabilities in craniopharyngioma. Neuro-Oncology. 2018;20:1101–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Rostami E, Witt Nystrom P, Libard S, Wikstrom J, Casar-Borota O, Gudjonsson O. Recurrent papillary craniopharyngioma with BRAFV600E mutation treated with neoadjuvant-targeted therapy. Acta Neurochir. 2017;159:2217–21.

    Article  PubMed  Google Scholar 

  55. Gao C, Wang Y, Broaddus R, Sun L, Xue F, Zhang W. Exon 3 mutations of CTNNB1 drive tumorigenesis: a review. Oncotarget. 2018;9:5492–508.

    PubMed  Google Scholar 

  56. Pavlidis ET, Pavlidis TE. Role of bevacizumab in colorectal cancer growth and its adverse effects: a review. World J Gastroenterol. 2013;19:5051–60.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  57. Gilbert MR, Dignam JJ, Armstrong TS, et al. A randomized trial of bevacizumab for newly diagnosed glioblastoma. N Engl J Med. 2014;370:699–708.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Long GV, Stroyakovskiy D, Gogas H, et al. Dabrafenib and trametinib versus dabrafenib and placebo for Val600 BRAF-mutant melanoma: a multicentre, double-blind, phase 3 randomised controlled trial. Lancet. 2015;386:444–51.

    Article  CAS  PubMed  Google Scholar 

  59. Eroglu Z, Ribas A. Combination therapy with BRAF and MEK inhibitors for melanoma: latest evidence and place in therapy. Ther Adv Med Oncol. 2016;8:48–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Brastianos PK, Shankar GM, Gill CM, et al. Dramatic response of BRAF V600E mutant papillary craniopharyngioma to targeted therapy. J Natl Cancer Inst. 2016;108

    Google Scholar 

  61. Aylwin SJ, Bodi I, Beaney R. Pronounced response of papillary craniopharyngioma to treatment with vemurafenib, a BRAF inhibitor. Pituitary. 2016;19:544–6.

    Article  PubMed  Google Scholar 

  62. Roque A, Odia Y. BRAF-V600E mutant papillary craniopharyngioma dramatically responds to combination BRAF and MEK inhibitors. CNS Oncol. 2017;6:95–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Himes BT, Ruff MW, Van Gompel JJ, et al. Recurrent papillary craniopharyngioma with BRAF V600E mutation treated with dabrafenib: case report. J Neurosurg. 2018:1–5.

    Google Scholar 

  64. Apps JR, Carreno G, Gonzalez-Meljem JM, et al. Tumour compartment transcriptomics demonstrates the activation of inflammatory and odontogenic programmes in human adamantinomatous craniopharyngioma and identifies the MAPK/ERK pathway as a novel therapeutic target. Acta Neuropathol. 2018;135:757–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

The authors thank Magnus Sundström, PhD, for his kind help with DNA analyses and for generating the pyrograms illustrating BRAF mutational status in the presented cases.

Author information

Authors and Affiliations

  1. Department of Neuroscience, Uppsala University, Uppsala, Sweden

    Elham Rostami & Olafur Gudjonsson

  2. Department of Neurosurgery, Uppsala University Hospital, Uppsala, Sweden

    Elham Rostami & Olafur Gudjonsson

  3. Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden

    Elham Rostami

  4. Department of Clinical Pathology, Uppsala University Hospital, Uppsala, Sweden

    Olivera Casar-Borota

  5. Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden

    Olivera Casar-Borota

Authors
  1. Elham Rostami
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Olivera Casar-Borota
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Olafur Gudjonsson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Elham Rostami .

Editor information

Editors and Affiliations

  1. Skull Base and Pituitary Neurosurgical Department, Hôpital Pierre Wertheimer “Groupement Hospitalier Est” Hospices Civils de Lyon“Claude Bernard” Lyon 1 University, Lyon, France

    Emmanuel Jouanneau

  2. Endocrinology Department, Reference Center for Rare Pituitary Diseases HYPO“Groupement Hospitalier Est” Hospices Civils de Lyon“Claude Bernard” Lyon 1 University, Lyon, France

    Gérald Raverot

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Rostami, E., Casar-Borota, O., Gudjonsson, O. (2020). Molecular Targets in Craniopharyngioma. In: Jouanneau, E., Raverot, G. (eds) Adult Craniopharyngiomas. Springer, Cham. https://doi.org/10.1007/978-3-030-41176-3_12

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-41176-3_12

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-41175-6

  • Online ISBN: 978-3-030-41176-3

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation