Skip to main content

Advertisement

SpringerLink
Log in

Delta-like protein (DLK) is a novel immunohistochemical marker for human hepatoblastomas

  • Original Article
  • Published:
Virchows Archiv Aims and scope Submit manuscript

Abstract

Delta-like protein (DLK) is a membrane protein with mostly unknown function. It is expressed by several embryonic tissues among others by the hepatoblasts of rodent and human fetal livers. We have investigated in the present study if this protein is expressed in human hepatoblastomas. The presence of DLK has been studied by standard immunohistochemistry in 31 hepatoblastomas and in several differential diagnostically related tumours: hepatocellular carcinomas and in undifferentiated childhood neoplasms. All the hepatoblastomas were positive for DLK; the surrounding liver tissue remained negative. The reaction was present in the epithelial component of the tumours. The staining pattern was mostly membranous, occasionally cytoplasmic. The other studied tumours were negative for DLK, except one hepatocellular carcinoma and the differentiating cells of two ganglioneuroblastomas. Therefore, DLK seems to be a highly sensitive and specific marker for hepatoblastomas.

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. l
Fig. 2

Similar content being viewed by others

Abbreviations

DLK:

delta-like protein

AFP:

alpha-fetoprotein

TLCT:

transitional liver cell tumour

MPNST:

malignant peripheral nerve sheath tumour

References

  1. Artavanis-Tsakonas S, Rand MD, Lake RJ (1999) Notch signalling: cell fate control and signal integration in developmentt. Science 284:770–776

    Article  PubMed  CAS  Google Scholar 

  2. Baladron V, Ruiz-Hidalgo MJ, Bonvini E, Gubina E, Notario V, Laborda J (2002) The EGF-like homeotic protein dlk affects cell growth and interacts with growth-modulating molecules in the yeast two hybrid system. Biochem Biophys Res Commun 291:193–204

    Article  PubMed  CAS  Google Scholar 

  3. Baladron V, Ruiz-Hidalgo MJ, Nueda ML, Diaz-Guerra MJ, Garcia-Ramirez JJ, Bonvini E, Gubina E, Laborda J (2005) Dlk acts as a negative regulator of NOTCH1 activation through interactions with specific EGF-like repeats. Exp Cell Res 303:343–359

    Article  PubMed  CAS  Google Scholar 

  4. Edmondson HA, Steiner PE (1954) Primary carcinoma of the liver. Cancer 7:462–503

    Article  PubMed  CAS  Google Scholar 

  5. Finegold MJ, Lopez-Terrada DH, Bowen J, Washington MK, Qualman SJ (2007) Protocol for the examination of specimens from pediatric patients with hepatoblastoma. Arch Pathol Lab Med 131:520–529

    PubMed  Google Scholar 

  6. Floridon V, Jensen CH, Thorsen P, Nielsen O, Sunde L, Westergaard JG, Thomsen SG, Teisner B (2000) Does fetal antigen 1 (FA1) identify cells with regenerative, endocrine and neuroendocrine potentials? A study of FA1 in embryonic, fetal, and placental tissue and maternal circulation. Differentiation 66:49–59

    Article  PubMed  CAS  Google Scholar 

  7. Hedlund GP, Carlsson HE, Shieck E, Nilsson I, Lundblad C, Arons S, Iversen AK, Looman C Jensen HE, Hau J (2003) Fetal antigen 1 (FA1) in the adult rat adrenal gland, ovary and pituitary gland. In Vivo 17:1–4

    PubMed  CAS  Google Scholar 

  8. Hsiao CC, Huang CC, Sheen JM, Tai MH, Chen CM, Huang LL, Chuang JH (2005) Differential expression of delta-like gene and protein in neuroblastoma, ganglioneuroblastoma and ganglioneuroma. Mod Pathol 18:656–662

    Article  PubMed  CAS  Google Scholar 

  9. Jensen CH, Jauho EI, Santoni-Rugiu E, Holmskov U, Teisner B, Tygstrup N, Bisgaard HC (2004) Transit-amplifying ductular (oval) cells and their hepatocytic progeny are characterized by a novel and distinctive expression of delta like protein/preadipocyte factor 1/fetal antigen 1. Am J Pathol 164:1347–1359

    PubMed  CAS  Google Scholar 

  10. Jelnes P, Santoni-Rugiu E, Rasmussen M, Friis SL, Nielsen JH, Tygstrup N, Bisgaard HC (2007) Remarkable phenotypic heterogeneity displayed by oval cells in rat and mouse models of stem cell-mediated liver regeneration. Hepatology 45:1462–147

    Article  PubMed  CAS  Google Scholar 

  11. Kiss A, Schnur J, Szabó Z, Nagy P (2001) Immunohistochemical analysis of atypical ductular reaction in the human liver, with special emphasis on the presence of growth factors and their receptors. Liver 21:237–246

    Article  PubMed  CAS  Google Scholar 

  12. Laborda J, Susville EA, Hoffman T, Notario V (1993) Dlk: a putative mammalian homeotic gene differentially expressed in small cell lung carcinoma and neuroendocrine tumor cell line. J Biol Chem 268:3817–3820

    PubMed  CAS  Google Scholar 

  13. Laborda J (2000) The role of the epidermal growth factor-like protein dlk in cell differentiation. Histol Histopathol 15:119–129

    PubMed  CAS  Google Scholar 

  14. Lee JS, Heo J, Libbrecht L, Chi I, Kaposi-Novák P, Calvisi DF, Mikaelyan A, Roberts LR, Demetris AJ, Sun Z, Nevens F, Roskams T, Thorgeirsson SS (2006) A novel prognostic subtype of human hepatocellular carcinoma derived from hepatic progenitor cells. Nat Med 12:410–416

    Article  PubMed  CAS  Google Scholar 

  15. Luo J, Ren B, Keryanov S, Tseng GC, Rao UNM, Monga SP, Strom S, Demetris AJ, Nalesnik M, Yu YP, Ranganathan S, Michalopoulos GK (2006) Transcriptomic and genomic analysis of human hepatocellular carcinomas and hepatoblastomas. Hepatology 44:1012–1024

    Article  PubMed  CAS  Google Scholar 

  16. Prokurat A, Kluge P, Kosciesza A (2002) Transitional liver cell tumours (TLCT) in older children and adolescents: a novel group of agressive hepatic tumours expressing beta-catenin. Med Pediatr Oncol 39:510–518

    Article  PubMed  Google Scholar 

  17. Roebuck DJ, Perilongo G (2006) Hepatoblastoma: an oncological review. Pediatr Radiol 36:183–186

    Article  PubMed  Google Scholar 

  18. Roskams TA, Theise ND, Balabaud C, Bhagat G, Bhathal PS, Bioulac-Sage P (2004) Nomenclature of the finer branches of the biliary tree: canals, ductules, and ductular reactions in human livers. Hepatology 39:1739–1745

    Article  PubMed  Google Scholar 

  19. Santoni-Rugiu E, Jelnes P, Thorgeirsson SS, Bisgaard HC (2005) Progenitor cells in liver regeneration: molecular responses controlling their activation and expansion. APMIS 113:876–902

    Article  PubMed  Google Scholar 

  20. Smas CM, Sul HS (1993) Pref-1, a protein containing EGF-like repeats, inhibits adipocyte differentiation. Cell 73:725–734

    Article  PubMed  CAS  Google Scholar 

  21. Tanimizu N, Miyajima A (2004a) Notch signaling controls hepatoblast differentiation by altering the expression of liver-enriched transcription factors. J Cell Sci 117:3165–3174

    Article  PubMed  CAS  Google Scholar 

  22. Tanimizu N, Tsujimura T, Takahide K, Kodama T, Nakamura K, Miyajima A (2004) Expression of Dlk/Pref-1 defines a subpopulation in the oval cell compartment of rat liver. Gene Expression Patterns 5:209–218

    Article  PubMed  CAS  Google Scholar 

  23. Tornehave D, Jensen CH, Teisner B, Larson LI (1996) FA1 immunreactivity in endocrine tumours and during development of the human fetal pancreas, negative correlation with glucagon expression. Histochem Cell Biol 106:535–542

    Article  PubMed  CAS  Google Scholar 

  24. Van Limpt VA, Chan AJ, Van Sluis PG (2003) High delta-like 1 expression in a subset of neuroblastoma cell lines corresponds to a differentiated chromaffin cell type. Int J Cancer 105:61–69

    Article  PubMed  Google Scholar 

  25. Zimmermann A (2005) The emerging family of hepatoblastoma tumours: from ontogenesis to oncogenesis. Eur J Cancer 41:1503–1514

    Article  PubMed  Google Scholar 

Download references

Acknowledgement

This study was supported by OTKA K 67697, TS 049887 and ETT 32/2006.

Conflict of interest statement

We declare that we have no conflict of interest.

Author information

Authors and Affiliations

  1. First Department of Pathology and Experimental Cancer Research, Semmelweis University, Üllõi út 26, Budapest, 1085, Hungary

    Katalin Dezső, Sándor Paku, Eszter Turányi & Peter Nagy

  2. Second Department of Pathology, Semmelweis University, Budapest, Hungary

    Judit Halász & Zsuzsa Schaff

  3. The Danish Stem Cell Research Centre, Department of Cellular and Molecular Medicine, The Panum Institute, University of Copenhagen, Copenhagen, Denmark

    Hanne Cathrine Bisgaard

Authors
  1. Katalin Dezső
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Judit Halász
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hanne Cathrine Bisgaard
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sándor Paku
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Eszter Turányi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Zsuzsa Schaff
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Peter Nagy
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Peter Nagy.

Additional information

K. D and J. H. contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dezső, K., Halász, J., Bisgaard, H.C. et al. Delta-like protein (DLK) is a novel immunohistochemical marker for human hepatoblastomas. Virchows Arch 452, 443–448 (2008). https://doi.org/10.1007/s00428-007-0571-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00428-007-0571-8

Keywords

Search

Navigation