Skip to main content

Advertisement

SpringerLink
Log in

Nuclear β-catenin accumulation associates with epithelial morphogenesis in craniopharyngiomas

  • Original Paper
  • Published:
Acta Neuropathologica Aims and scope Submit manuscript

Abstract

Activation of the Wnt/wingless signalling cascade is a key mechanism in developmental morphogenesis, whereas aberrant nuclear accumulation of β-catenin in adult tissues seems to be associated with neoplastic transformation and tumour progression. Adamantinomatous craniopharyngiomas carry activating mutations in exon 3 of the β-catenin gene, which results in a distinct pattern of nuclear β-catenin accumulation in up to 95% of respective tumour specimens. To better characterise the impact of nuclear β-catenin aggregation in these neoplasms, we systematically examined epithelial differentiation and cell cycle-associated molecules in accumulating compared to non-accumulating tumour cell clusters using a cohort of 65 adamantinomatous craniopharyngiomas. Monoclonal antibodies directed against cytokeratins 5/6 (CK5/6) were utilised to differentiate squamous from simple epithelium, the latter being identified by immunoreactivity for cytokeratins 8 and 18 (CK8/CK18). Intriguingly, nuclear β-catenin accumulation in whorl-like tumour cell clusters was always associated with a distinct CK8 and CK18 immunoreactivity, whereas surrounding non-accumulating tumour cells showed exclusively squamous differentiation indicated by CK5/6 expression. In addition, a low proliferation activity combined with an increased expression of p21WAF1/CIP1, a key control protein of the cell cycle, was observed in β-catenin accumulating cells. Our data support an impact of nuclear β-catenin on different cytoarchitectural and epithelial differentiation patterns in adamantinomatous craniopharyngiomas.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Asa SL, Kovacs K, Bilbao JM, Penz G (1981) Immunohistochemical localization of keratin in craniopharyngiomas and squamous cell nests of the human pituitary. Acta Neuropathol (Berl) 54:257–260

    Article  CAS  Google Scholar 

  2. Blumenberg M (1988) Concerted gene duplications in the two keratin gene families. J Mol Evol 27:203–211

    Article  CAS  PubMed  Google Scholar 

  3. Brabletz T, Jung A, Reu S, Porzner M, Hlubek F, Kunz-Schughart LA, Knuechel R, Kirchner T (2001) Variable beta-catenin expression in colorectal cancers indicates tumor progression driven by the tumor environment. Proc Natl Acad Sci USA 98:10356–10361

    Article  CAS  PubMed  Google Scholar 

  4. Buslei R, Nolde M, Hofmann B, Meissner S, Eyupoglu IY, Siebzehnrubl F, Hahnen E, Kreutzer J, Fahlbusch R (2005) Common mutations of beta-catenin in adamantinomatous craniopharyngiomas but not in other tumours originating from the sellar region. Acta Neuropathol (Berl) 109:589–597

    Article  CAS  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  6. Fahlbusch R, Honegger J, Paulus W, Huk W, Buchfelder M (1999) Surgical treatment of craniopharyngiomas: experience with 168 patients. J Neurosurg 90:237–250

    Article  CAS  PubMed  Google Scholar 

  7. Ghatak NR, Hirano A, Zimmerman HM (1971) Ultrastructure of a craniopharyngioma. Cancer 27:1465–1475

    Article  CAS  PubMed  Google Scholar 

  8. Hassanein AM, Glanz SM, Kessler HP, Eskin TA, Liu C (2003) beta-Catenin is expressed aberrantly in tumors expressing shadow cells. Pilomatricoma, craniopharyngioma, and calcifying odontogenic cyst. Am J Clin Pathol 120:732–736

    Article  CAS  PubMed  Google Scholar 

  9. Hofmann BM, Kreutzer J, Saeger W, Buchfelder M, Bluemcke I, Fahlbusch R, Buslei R (2006) Nuclear β-catenin accumulation as reliable marker for the differentiation between cystic craniopharyngiomas and Rathke’s cleft cysts: a clinico-pathological approach. Am J Surg Pathol (in press)

  10. Jackson BW, Grund C, Schmid E, Burki K, Franke WW, Illmensee K (1980) Formation of cytoskeletal elements during mouse embryogenesis. Intermediate filaments of the cytokeratin type and desmosomes in preimplantation embryos. Differentiation 17:161–179

    Article  CAS  PubMed  Google Scholar 

  11. Kato K, Nakatani Y, Kanno H, Inayama Y, Ijiri R, Nagahara N, Miyake T, Tanaka M, Ito Y, Aida N, Tachibana K, Sekido K, Tanaka Y (2004) Possible linkage between specific histological structures and aberrant reactivation of the Wnt pathway in adamantinomatous craniopharyngioma. J Pathol 203:814–821

    Article  CAS  PubMed  Google Scholar 

  12. Kirchner T, Brabletz T (2000) Patterning and nuclear beta-catenin expression in the colonic adenoma-carcinoma sequence. Analogies with embryonic gastrulation. Am J Pathol 157:1113–1121

    CAS  PubMed  Google Scholar 

  13. Kirchner T, Muller S, Hattori T, Mukaisyo K, Papadopoulos T, Brabletz T, Jung A (2001) Metaplasia, intraepithelial neoplasia and early cancer of the stomach are related to dedifferentiated epithelial cells defined by cytokeratin-7 expression in gastritis. Virchows Arch 439:512–522

    Article  CAS  PubMed  Google Scholar 

  14. Kleihues P, Cavenee WK (2000) Pathology & genetics tumours of the nervous system. IARC Press, Lyon

    Google Scholar 

  15. Kurosaki M, Saeger W, Ludecke DK (2001) Immunohistochemical localisation of cytokeratins in craniopharyngioma. Acta Neurochir (Wien) 143:147–151

    Article  CAS  Google Scholar 

  16. Mariadason JM, Bordonaro M, Aslam F, Shi L, Kuraguchi M, Velcich A, Augenlicht LH (2001) Down-regulation of beta-catenin TCF signaling is linked to colonic epithelial cell differentiation. Cancer Res 61:3465–3471

    CAS  PubMed  Google Scholar 

  17. Markey AC, Lane EB, Churchill LJ, MacDonald DM, Leigh IM (1991) Expression of simple epithelial keratins 8 and 18 in epidermal neoplasia. J Invest Dermatol 97:763–770

    Article  CAS  PubMed  Google Scholar 

  18. Miyoshi K, Rosner A, Nozawa M, Byrd C, Morgan F, Landesman-Bollag E, Xu X, Seldin DC, Schmidt EV, Taketo MM, Robinson GW, Cardiff RD, Hennighausen L (2002) Activation of different Wnt/beta-catenin signaling components in mammary epithelium induces transdifferentiation and the formation of pilar tumors. Oncogene 21:5548–5556

    Article  CAS  PubMed  Google Scholar 

  19. Miyoshi K, Shillingford JM, Le Provost F, Gounari F, Bronson R, von Boehmer H, Taketo MM, Cardiff RD, Hennighausen L, Khazaie K (2002) Activation of beta -catenin signaling in differentiated mammary secretory cells induces transdifferentiation into epidermis and squamous metaplasias. Proc Natl Acad Sci USA 99:219–224

    Article  CAS  PubMed  Google Scholar 

  20. Moll R, Franke WW, Schiller DL, Geiger B, Krepler R (1982) The catalog of human cytokeratins: patterns of expression in normal epithelia, tumors and cultured cells. Cell 31:11–24

    Article  CAS  PubMed  Google Scholar 

  21. Naishiro Y, Yamada T, Takaoka AS, Hayashi R, Hasegawa F, Imai K, Hirohashi S (2001) Restoration of epithelial cell polarity in a colorectal cancer cell line by suppression of beta-catenin/T-cell factor 4-mediated gene transactivation. Cancer Res 61:2751–2758

    CAS  PubMed  Google Scholar 

  22. Owens DW, Lane EB (2003) The quest for the function of simple epithelial keratins. Bioessays 25:748–758

    Article  CAS  PubMed  Google Scholar 

  23. Polakis P (2000) Wnt signaling and cancer. Genes Dev 14:1837–1851

    CAS  PubMed  Google Scholar 

  24. Saegusa M, Hashimura M, Kuwata T, Hamano M, Okayasu I (2004) Beta-catenin simultaneously induces activation of the p53-p21WAF1 pathway and overexpression of cyclin D1 during squamous differentiation of endometrial carcinoma cells. Am J Pathol 164:1739–1749

    CAS  PubMed  Google Scholar 

  25. Schaafsma HE, Ramaekers FC, van Muijen GN, Lane EB, Leigh IM, Robben H, Huijsmans A, Ooms EC, Ruiter DJ (1990) Distribution of cytokeratin polypeptides in human transitional cell carcinomas, with special emphasis on changing expression patterns during tumor progression. Am J Pathol 136:329–343

    CAS  PubMed  Google Scholar 

  26. Seemayer TA, Blundell JS, Wiglesworth FW (1972) Pituitary craniopharyngioma with tooth formation. Cancer 29:423–430

    Article  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  28. 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 45:573–579

    Article  CAS  PubMed  Google Scholar 

  29. Tateyama H, Tada T, Okabe M, Takahashi E, Eimoto T (2001) Different keratin profiles in craniopharyngioma subtypes and ameloblastomas. Pathol Res Pract 197:735–742

    Article  CAS  PubMed  Google Scholar 

  30. Wikramanayake AH, Hong M, Lee PN, Pang K, Byrum CA, Bince JM, Xu R, Martindale MQ (2003) An ancient role for nuclear beta-catenin in the evolution of axial polarity and germ layer segregation. Nature 426:446–450

    Article  CAS  PubMed  Google Scholar 

  31. Xin W, Rubin MA, McKeever PE (2002) Differential expression of cytokeratins 8 and 20 distinguishes craniopharyngioma from Rathke cleft cyst. Arch Pathol Lab Med 126:1174–1178

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank S. Gutmann, B. Rings, A. Schindler and C. Winkelmann for expert technical assistance. We thank Dr. T. Brabletz (Univ. of Erlangen, Germany) for helpful discussions. This work was supported by ELAN and Marohn funds from the University of Erlangen Medical Faculty.

Author information

Authors and Affiliations

  1. Department of Neuropathology, Friedrich-Alexander University Erlangen-Nuremberg, Krankenhausstrasse 8-10, 91054, Erlangen, Germany

    Rolf Buslei, Annett Hölsken, Florian Siebzehnrubl & Ingmar Blümcke

  2. Department of Neurosurgery, Friedrich-Alexander University of Erlangen-Nuremberg, Erlangen, Germany

    Bernd Hofmann, Jürgen Kreutzer & Michael Buchfelder

  3. Department of Neuropathology, Evangelic Hospital Bielefeld, Bielefeld, Germany

    Volkmar Hans

  4. Department of Neurosurgery, Evangelic Hospital Bielefeld, Bielefeld, Germany

    Falk Oppel

  5. International Neuroscience Institute, Hannover, Germany

    Rudolf Fahlbusch

Authors
  1. Rolf Buslei
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Annett Hölsken
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bernd Hofmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jürgen Kreutzer
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Florian Siebzehnrubl
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Volkmar Hans
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Falk Oppel
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Michael Buchfelder
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Rudolf Fahlbusch
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Ingmar Blümcke
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rolf Buslei.

Additional information

This work is supported by the Johannes and Frieda Marohn Foundation (to RB and BH).

Rights and permissions

Reprints and permissions

About this article

Cite this article

Buslei, R., Hölsken, A., Hofmann, B. et al. Nuclear β-catenin accumulation associates with epithelial morphogenesis in craniopharyngiomas. Acta Neuropathol 113, 585–590 (2007). https://doi.org/10.1007/s00401-006-0184-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00401-006-0184-3

Keywords

Search

Navigation