Skip to main content

Advertisement

SpringerLink
Log in

CD24 Expression is an Independent Prognostic Marker in Cholangiocarcinoma

  • Published:
Journal of Gastrointestinal Surgery

Abstract

CD24 has been described as an adverse prognostic marker in several malignancies. This study evaluates CD24 expression in cholangiocarcinoma and correlates the findings with clinicopathologic data and patient survival. Between 1996 and 2002, 22 consecutive patients with cholangiocarcinoma were treated at our institution. Demographic data, SEER stage, pathologic data, treatment, expression of CD24, mitogen-activated protein kinase (MAPK), phosphorylated MAPK, and survival were analyzed. The majority of the tumors demonstrated CD24 (81.8%) and p-MAPK (87%) expression. A negative association was noted between the expression of CD24 and p-MAPK. Median survival for patients with low expression of CD24 was 36 months and high expression was 8 months. Median survival for patients who received chemotherapy with low CD24 expression was 163 months, and for seven patients with high CD24 expression, it was 17 months (p = 0.04). With the addition of radiation therapy, median survival for patients with low expression of CD24 was 52 months and high expression was 17 months (p = 0.08). On multivariate analysis, the use of chemotherapy (p = 0.0014, hazard ratio 0.069) and the CD24 overexpression (p = 0.02, hazard ratio 7.528) were predictive of survival. CD24 is commonly expressed in cholangiocarcinoma, and overexpression is predictive of poor survival and possibly of lack of response to chemotherapy and radiation therapy. These findings may improve selection of patients for the appropriate treatment modality and the development of CD24-targeted therapy.

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

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  1. Burke EC, Jarnagin WR, Hochwald SN, Pisters PW, Fong Y, Blumgart LH. Hilar cholangiocarcinoma: patterns of spread, importance of hepatic resection for curative operation and a presurgical clinical staging system. Ann Surg 1998;228:385–394.

    Article  PubMed  CAS  Google Scholar 

  2. Nagorney DM, Donohue JH, Farnell MB, Schleck CD, Ilstrup DM. Outcomes after curative resections of cholangiocarcinoma. Arch Surg 1993;128(8):871–877.

    PubMed  CAS  Google Scholar 

  3. Klempnauer J, Rideer GJ, von Wasielewski R, Werner M, Weimann A, Pichmayr R. Resectional surgery of hilar cholangiocarcinoma: a multivariate analysis of prognostic factors. J Clin Oncol 1997;15(3):947–954.

    PubMed  CAS  Google Scholar 

  4. Abdel Wahab M, Fathy O, Elghwalby N, Sultan A, Elebidy E, Abdalla T, Elshobary M, Mostafa M, Foad A, Kandeel T, Abdel Raouf A, Salah T, Abu Zeid M, Abu Elenein A, Gad Elhak N, ElFiky A, Ezzat F. Resectability and prognostic factors after resection of hilar cholangiocarcinoma. Hepatogastroenterology 2006;53(67):5–10.

    PubMed  CAS  Google Scholar 

  5. Ebata T, Nagino M, Kamiya J, Uesaka K, Nagasaka T, Nimura Y. Hepatectomy with portal vein resection for hilar cholangiocarcinoma: audit of 52 consecutive cases. Ann Surg 2003;238(5):720–727.

    Article  PubMed  Google Scholar 

  6. Shirabe K, Shimada M, Tsujita E et al. Prognostic factors in node-negative intrahepatic cholangiocarcinoma with special reference to angiogenesis. Am J Surg 2004;187(4):538–542.

    Article  PubMed  Google Scholar 

  7. Abou-Rebyeh H, Al-Abadi H, Jonas S, Rotter I, Bechstein WO, Neuhaus P. DNA analysis of cholangiocarcinoma cells: prognostic and clinical importance. Cancer Detect Prev 2002;26(4):313–319.

    Article  PubMed  CAS  Google Scholar 

  8. Su MC, Hsu C, Kao HL, Jeng YM. CD24 expression is a prognostic factor in intrahepatic cholangiocarcinoma. Cancer Lett 2006;235(1):34–349.

    Article  PubMed  CAS  Google Scholar 

  9. Xiao M, Zhou NX, Huang ZQ, Lu YL, Chen LH, Wang DJ, Chang WL. The ratio of MMP-2 to TIMP-2 in hilar cholangiocarcinoma: a semi-quantitative study. Hepatobiliary Pancreat Dis Int 2004;3(4):599–602.

    PubMed  CAS  Google Scholar 

  10. Hamamoto Y, Niino K, Ishiyama H, Hosoya T. Impact of pretreatment cholinesterase level on survival of inoperable intrahepatic or hepatic–hilar carcinomas treated with three-dimensional conformal radiotherapy. Radiat Med 2004;22(5):316–323.

    PubMed  Google Scholar 

  11. Shibahara H, Tamada S, Higashi M, Goto M, Batra SK, Imai K, Yonezawa S. MUC4 is a novel prognostic factor of intrahepatic cholangiocarcinoma-mass forming type. Hepatology 2004;39(1):220–229.

    Article  PubMed  CAS  Google Scholar 

  12. Sugimachi K, Aishima S, Taguchi K, Tanaka S, Shimada M, Kajiyama K, Sugimachi K, Tsuneyoshi M. The role of overexpression and gene amplification of cyclin D1 in intrahepatic cholangiocarcinoma. J Hepatol 2001;35(1):74–79.

    Article  PubMed  CAS  Google Scholar 

  13. Park BK, Paik YH, Park JY, Park KH, Bang S, Park SW, Chung JB, Park YN, Song SY. The clinicopathologic significance of the expression of vascular endothelial growth factor-C in intrahepatic cholangiocarcinoma. Am J Clin Oncol 2006;29(2):138–142.

    Article  PubMed  CAS  Google Scholar 

  14. Fiorentino M, Altimari A, D’Errico A, Gabusi E, Chieco P, Masetti M, Grigioni WF. Low p27 expression is an independent predictor of survival for patients with either hilar or peripheral intrahepatic cholangiocarcinoma. Clin Cancer Res 2001;7(12):3994–3999.

    PubMed  CAS  Google Scholar 

  15. Tannapfel A, Engeland K, Weinans L, Katalinic A, Hauss J, Mossner J, Wittekind C. Expression of p73, a novel protein related to the p53 tumour suppressor p53, and apoptosis in cholangiocellular carcinoma of the liver. Br J Cancer 1999;80(7):1069–1074.

    Article  PubMed  CAS  Google Scholar 

  16. Weichert W, Denkert C, Burkhardt M, Gansukh T, Bellach J, Altevogt P, Dietel M, Kristansen G. Cytoplasmic CD24 expression in colorectal cancer independently correlates with shortened patient survival. Clin Cancer Res 2005;11(18):6572–6581.

    Article  Google Scholar 

  17. Lim SC, Oh SH. The role of CD24 in various human epithelial neoplasias. Pathol Res Pract 2005;201(7):479–486.

    Article  PubMed  CAS  Google Scholar 

  18. Kristiansen G, Schluns K, Yongwei Y, Denkert C, Dietel M, Petersen I. CD24 is an independent prognostic marker of survival in nonsmall cell lung cancer patients. Brit J Cancer 2003;88:231–236.

    Article  PubMed  CAS  Google Scholar 

  19. Kristiansen G, Pilarsky C, Pervan J, Sturzebecher B, Stephan C, Jung K, Loening S, Rosenthal A, Dietel M. CD24 expression is a significant predictor of PSA relapse and poor prognosis in low grade or organ confined prostate cancer. Prostate 2004;58:183–192.

    Article  PubMed  Google Scholar 

  20. Kristiansen G, Denkert C, Schluns K, Dahl E, Pilarsky C, Hauptmann S. CD24 is expressed in ovarian cancer and is a new independent prognostic marker of patient survival. Am J Pathol 2002;161(4):1215–1221.

    PubMed  CAS  Google Scholar 

  21. Kristiansen G, Winzer KJ, Mayordomo E, Bellach J, Schluns K, Denkert C, Dahl E, Pilarsky C, Altevogt P, Guski H, Dietel M. CD24 expression is a new prognostic marker in breast cancer. Clin Cancer Res 2003;9:4906–4913.

    PubMed  CAS  Google Scholar 

  22. Pirrucello SJ, LeBien TW. The human B cell-association antigen CD24 is a single chain sialoglycoprotein. J Immunol 1986;136:3779–3784.

    Google Scholar 

  23. Fischer GF, Majdic O, Gadd S, Knapp W. Signal transduction in lymphocytic and myeloid cells via CD24, a new member of phosphoinositol-anchored membrane molecules. J Immunol 1990;144:638–641.

    PubMed  CAS  Google Scholar 

  24. Akashi T, Shirasawa T, Hirokawa K. Gene expression of CD24 core polypeptide molecule in normal rat tissues and human tumor cell lines. Virchows Arch 1994;425:399–406.

    Article  PubMed  CAS  Google Scholar 

  25. Aigner S, Ruppert M, Hubbe M, Sammar M, Sthoeger Z, Butcher EC, Vestweber D, Altevogt P. Heat stable antigen (mouse CD24) supports myeloid cell binding to endothelial and platelet P-selectin. Int Immunol 1995;7(10):1557–1565.

    Article  PubMed  CAS  Google Scholar 

  26. Aigner S, Sthoeger ZM, Fogel M, Weber E, Zarn J, Ruppert M, Zeller Y, Vestweber D, Stahel R, Sammar M, Altevogt P. CD24 a mucin-type glycoprotein is a ligand for P-selectin on human tumor cells. Blood 1997;89(9):3385–3395.

    PubMed  CAS  Google Scholar 

  27. Aigner S, Ramos CL, Hafezi-Moghadam A, Lawrence MB, Friederichs J, Altevogt P, Ley K. CD24 mediates rolling of breast carcinoma cells on P-selectin. FASEB J 1998;12(12):1241–1251.

    PubMed  CAS  Google Scholar 

  28. Friederichs J, Zeller Y, Hafezi-Moghadam A, Grone HJ, Ley K, Altevogt P. The CD24/P-selectin binding pathway initiates lung arrest of human A125 adenocarcinoma cells. Cancer Res 2000;60(23):6714–6722.

    PubMed  CAS  Google Scholar 

  29. Taguchi T, Kiyokawa N, Mimori K, Suzuki T, Sekino T, Nakajima H, Saito M, Katagiri YU, Matsuo N, Matsuo Y, Karasuyama H, Fujimoto J. Pre-B cell antigen receptor-mediated signal inhibits CD24-induced apoptosis in human pre-B cells. J Immunol 2003;170(1):252–260.

    PubMed  CAS  Google Scholar 

  30. Malik SN, Brattain M, Ghosh PM, Troyer DA, Prihoda R, Bedolla R, Kreisberg JI. Immunohistochemical demonstration of phospho-Akt in high Gleason grade prostate cancer. Clin Cancer Res 2002;8:1168–1171.

    PubMed  Google Scholar 

  31. Baumann P, Cremers N, Kroese F, Orend G, Chiquet-Ehrismann R, Uede T, Yaqita H, Sleeman JP. CD24 expression causes the acquisition of multiple cellular properties associated with tumor growth and metastasis. Cancer Res 2005;65(23):10783–10793.

    Article  PubMed  CAS  Google Scholar 

  32. Smith SC, Oxford G, Wu Z, Nitz MD, Conaway M, Frierson HF, Hampton G, Theodorescu D. The metastasis-associated gene CD24 is regulated by Ral GTPase and is a mediator of cell proliferation and survival in human cancer. Cancer Res 2006;66(4):1917–1922.

    Article  PubMed  CAS  Google Scholar 

  33. Javle MM, Yu J, Khoury T. AKT expression may predict favorable prognosis in cholangiocarcinoma. J Gastroenterol Hepatol 21:1744–1751.

  34. Uckun FM, Song CW. Lack of CD24 antigen expression in B-lineage acute lymphoblastic leukemia is associated with intrinsic radiation resistance of primary clonogenic blasts. Blood 1993;81(5):1323–1332.

    PubMed  CAS  Google Scholar 

  35. Weber E, Schmitter D, Resch H, Zarn JA, Waibel R, Mabry M, Huquenin P, Stahel RA. Radiation studies on B cell differentiation marker CD24/SCLC Cluster-4 antigen expressing and non-expressing lung cancer cell lines and mouse fibroblasts. Int J Radiat Biol 1995;68(2):205–213.

    PubMed  CAS  Google Scholar 

  36. Nordsmark M, Overgaard J. Tumor hypoxia is independent of hemoglobin and prognostic for loco-regional tumor control after primary radiotherapy in advanced head and neck cancer. Acta Oncol 2004;43(4):396–403.

    Article  PubMed  Google Scholar 

  37. Rofstad EK, Sundfor K, Trope CG. Hypoxia-induced treatment failure in advanced squamous cell carcinoma of the uterine cervix is primarily due to hypoxia-induced radiation resistance rather than hypoxia-induced metastasis. Br J Cancer 2000;83(3):354–359.

    Article  PubMed  CAS  Google Scholar 

  38. Yokoi K, Fidler IJ. Hypoxia increases resistance of human pancreatic cancer cells to apoptosis induced by gemcitabine. Clin Cancer Res 2004;10(7):2299–2306.

    Article  PubMed  CAS  Google Scholar 

  39. Koch S, Mayer F, Honecker F, Schittenhelm M, Bokemeyer C. Efficacy of cytotoxic agents used in the treatment of testicular germ cell tumours under normoxic and hypoxic conditions in vitro. Br J Cancer 2003;89(11):2133–2139.

    Article  PubMed  CAS  Google Scholar 

  40. Scheurer SB, Rybak JN, Rosli C, Neri D, Elia G. Modulation of gene expression by hypoxia in human umbilical cord vein endothelial cells: a transcriptomic and proteomic study. Proteomics 2004;4:1737–1760.

    Article  PubMed  CAS  Google Scholar 

  41. Pitt HA, Nakeeb A, Abrams RA et al. Perihilar cholangiocarcinoma: postoperative radiotherapy does not improve survival. Ann Surg 1995;221(6):788–798.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Surgical Oncology, Roswell Park Cancer Institute, State University of New York, Elm and Carlton Streets, Buffalo, NY, 14263, USA

    Shefali Agrawal, Boris W. Kuvshinoff & John F. Gibbs

  2. Department of Pathology, Roswell Park Cancer Institute, State University of New York, Buffalo, NY, USA

    Thaer Khoury, Charles LeVea & Jeff Groth

  3. Department of Biostatistics, Roswell Park Cancer Institute, State University of New York, Buffalo, NY, USA

    Jihnhee Yu

  4. Department of Medical Oncology, Roswell Park Cancer Institute, State University of New York, Buffalo, NY, USA

    Milind M. Javle

  5. Department of Cancer Genetics, Roswell Park Cancer Institute, State University of New York, Buffalo, NY, USA

    Lionel J. Coignet

Authors
  1. Shefali Agrawal
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Boris W. Kuvshinoff
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Thaer Khoury
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jihnhee Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Milind M. Javle
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Charles LeVea
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jeff Groth
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Lionel J. Coignet
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. John F. Gibbs
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to John F. Gibbs.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Agrawal, S., Kuvshinoff, B.W., Khoury, T. et al. CD24 Expression is an Independent Prognostic Marker in Cholangiocarcinoma. J Gastrointest Surg 11, 445–451 (2007). https://doi.org/10.1007/s11605-007-0091-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11605-007-0091-5

Keywords

Search

Navigation