Skip to main content
SpringerLink
Log in

Evaluation of squamous cell carcinoma antigen-immunoglobulin M complex (SCCA-IGM) and alpha-l-fucosidase (AFU) as novel diagnostic biomarkers for hepatocellular carcinoma

  • Research Article
  • Published:
Tumor Biology

Abstract

Hepatocellular carcinoma (HCC) surveillance lacks a reliable biomarker. Alpha-fetoprotein (AFP) is the most widely used. However, not all HCCs secrete AFP. AFP may be elevated with cirrhosis in the absence of HCC. Serum alpha-l-fucosidase (AFU) and squamous cell carcinoma antigen-immunoglobulin M complex (SCCA-IgM) were found to be useful markers in diagnosing HCC. SCCA-IgM and AFU were assessed by ELISA technique; AFP was measured by enzyme chemiluminescence in serum of 40 patients with HCC, 30 patients with liver cirrhosis, and 20 healthy control participants to compare their accuracy in early diagnosis of HCC. Serum SCCA-IgM and AFU levels were significantly elevated in HCC group compared to cirrhotic group (P value < 0.001 and <0.001, respectively). Receiver operating characteristic curve showed the optimal cutoff value for SCCA-IgM was 233 AU/ml with sensitivity 87.5 % and specificity 66 % and for AFU was 25 U/L with sensitivity 87.5 % and specificity 98 %. AFP cutoff value was 48 ng/mL with sensitivity of 70 % and specificity of 53.3 %. The simultaneous determination of AFP and SCCA-IgM activity increased the sensitivity to 92.5 % and specificity to 62.1 %. There were positive significant correlations between SCCA-IgM and each of AFU (r = 0.296, P = 0.005) and AFP (r = 0.284, P = 0.007) and no correlation between AFP and AFU. All markers did not correlate with the tumor size or affected by the Child score. The significant difference between SCCA-IgM and AFU levels among HCC and cirrhotic patients suggests their use as potential diagnostic tools and allows identifying a new group of HCC patients even in the absence of elevated AFP.

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

Similar content being viewed by others

References

  1. Abdelaziz AO, Elbaz TM, Shousha HI, Ibrahim MM, Elshazli MA, Abdelmaksoud AH, et al. Survival and prognostic factors for hepatocellular carcinoma: an Egyptian multidisciplinary clinic experience. Asian Pac J Cancer Prev. 2014;15(9):3915–20.

    Article  PubMed  Google Scholar 

  2. Freedman S, Edwards K, Ries G, Young L. Cancer incidence in four member countries (Cyprus, Egypt, Israel, and Jordan) of the Middle East Cancer Consortium (MECC) compared with US SEER. National Cancer Institute. Bethesda 2006; 06–5873.

  3. Lok AS, Sterling RK, Everhart JE, Wright EC, Hoefs JC, Di Bisceglie AM, et al. Des-gamma-carboxy prothrombin and alpha-fetoprotein as biomarkers for the early detection of hepatocellular carcinoma. Gastroenterology. 2010;138(2):493–502.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  4. Giannelli G, Marinosci F, Sgarra C, Lupo L, Dentico P, Antonaci S. Clinical role of tissue and serum levels of SCCA antigen in hepatocellular carcinoma. Int J Cancer. 2005; 579–83.

  5. Buccione D, Fatti G, Gallotta A, Loggi E, Roberto G, Testa L, et al. Serum SCCA-IgM as a predictor of hepatocellular carcinoma in patients with liver cirrhosis. Gastroenterology. 2012;2:56–61.

    CAS  Google Scholar 

  6. Zuin J, Veggiani G, Pengo P, Gallotta A, Biasiolo A, Tono N, et al. Experimental validation of specificity of the squamous cell carcinoma antigen-immunoglobulin M (SCCA-IgM) assay in patients with cirrhosis. Clin Chem Lab Med. 2010;48(2):217–23.

    Article  CAS  PubMed  Google Scholar 

  7. Teofenescu I, Gologan E, Stefanescu G, Balan G. Surveillance of cirrhosis for hepatocellular carcinoma-clinical validation of new serological biomarkers for improved HEBA hepatocellular carcinoma diagnosis. Rev Med Chir Soc Med Nat lasi. 2010;114(1):39–46.

    Google Scholar 

  8. Gameel M, El assaly, N, Madani H, El-Ashry N, Mostafa, Abd El Raof, E and El-Rasky. Evaluation of tumor markers panel in detection of HCC in HCV Egyptian patients and its correlation with AFT M. Research Journal of Medicine and Medical sciences. 2009; 4 (2): 402–410.

  9. Bruix J, Sherman M, American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma: an update. Hepatology. 2011;53(3):1020–2.

    Article  PubMed Central  PubMed  Google Scholar 

  10. Cordero O, Ana M, Nogueira M, Vicenta S. Cell surface human alpha-L-fucosidase. Eur J Biochem. 2001;268:3321–31.

    Article  CAS  PubMed  Google Scholar 

  11. Pontisso P, Quarta S, Caberlotto C, Beneduce L, Marino M, Bernardinello E, et al. Progressive increase of SCCA-IgM immune complexes in cirrhotic patients is associated with development of hepatocellular carcinoma. Int J Cancer. 2006;119:735–40.

    Article  CAS  PubMed  Google Scholar 

  12. Dengnier Y, David V, Brissot P, Leray G, Blayau M, Le Gall JY. Serum alpha-L-fucocidase: a new marker for the diagnosis of primary hepatocellular carcinoma. Hepatology. 1984;4:889–92.

    Article  Google Scholar 

  13. Hutchinson WL, Johnson PJ, Du MQ, Williams R. Serum and tissue alpha-L-fucosidase activity in the pre-clinical and clinical stages of hepatocellular carcinoma. Clin Sci (Lond). 1991;81(2):177–82.

    CAS  Google Scholar 

  14. Wang J, Cao E. Rapid kinetic rate assay of the serum α-L-fucosidase in patients with hepatocellular carcinoma by using a novel substrate. Clinica Chimica Acta. 2004; (347):103–109.

  15. El-Shahawia M, Othmanb A, El-Houseinic M, Nashedd B, Elsofyd M. Spectrofluorimetric method for measuring the activity of the enzyme-l-fucosidase using the ion associate of 2-chloro-4-nitro phenol-rhodamine-B. Talanta. 2009; 15; 80 (1):19–23.

  16. Giardina G, Matarazzo M, Morante R, Lucariello A, Varriale A, Gulidasole V, et al., Serum alpha-L-fucosidase activity and early detection of hepatocellular carcinoma. Cancer. 1998; (83) 2468– 74.

  17. Cuer M, Barnier A, de La Salmoniere P, Durand G, and Seta N. Fluorimetric measurement of plasma alpha-L-fucosidase activity with a centrifugal analyzer: reference values in a healthy French adult population. Clin Chem. 2000; (46) 560a– 70a.

  18. Montaser MF, Sakr MA, Khalifa MO. Alpha-l-fucosidase as a tumour marker of hepatocellular carcinoma. Arab J Gastroenterol. 2012;13(1):9–13.

    Article  Google Scholar 

  19. Malaguarnera G, Giordano M, Paladina I, Berretta M, Cappellani A, Malaguarnera M. Serum markers of hepatocellular carcinoma. Dig Dis Sci. 2010;55(10):2744–55.

    Article  CAS  PubMed  Google Scholar 

  20. Bertino G, Ardiri A, Malaguarnera M, Malaguarnera G, Bertino N, Calvagno GS. Hepatocellualar carcinoma serum markers. Semin Oncol. 2012;39(4):410–33.

    Article  CAS  PubMed  Google Scholar 

  21. Savitskaya YA, Rico G, Linares L, González R, Tċéllez R, Estrada E, Marín N, Martínez E, Alfaro A, Ibarra C. Circulating natural IgM antibodies against angiogenin in the peripheral blood sera of patients with osteosarcoma as candidate biomarkers and reporters of tumorigenesis. Biomarkers in cancer. 2012;(2) 65-78.

  22. Trerotoli P, Fransvea E, Angelotti U, Antonaci G, Lupo L, Mazzocca A, et al. Tissue expression of squamous cellular carcinoma antigen (SCCA) is inversely correlated to tumor size in HCC. Mol Cancer. 2009;8:29.

    Article  PubMed Central  PubMed  Google Scholar 

  23. Schmilovitz-Weiss H, Tobar A, Halpern M, Levy I, Shabtai E. Tissue expression of squamous cellular carcinoma antigen and Ki67 in hepatocellular carcinoma-correlation with prognosis: a historical prospective study. Diagn Pathol. 2011;6:121.

    Article  PubMed Central  PubMed  Google Scholar 

  24. Pozzan C, Cardin R, Piciocchi M, Cazzagon NMaddalo G, Vanin V, Giacomin A, Pontisso P, Cillo U, Farinati F. Diagnostic and prognostic role of Scca-Igm serum levels in hepatocellular carcinoma (Hcc). J Gastroenterol Hepatol. 2014. doi: 10.1111/jgh.12576. [Epub ahead of print].

  25. Giannini EG1, Basso M Bazzica M Contini P, Marenco S, Savarino V, Picciotto A. Successful antiviral therapy determines a significant decrease in squamous cell carcinoma antigen-associated (SCCA) variants' serum levels in anti-HCV positive cirrhotic patients. J Viral Hepat. 2010 Aug;17 (8):563–8.

  26. Beneduce L, Castaldi F, Marino M, Quarta S, Ruvoletto M, Benvegnứ L, Calabrese F, Gatta A, Pontisso P, Fassina G. Squamous cell carcinoma antigen–immunoglobulin M complexes as novel biomarkers for hepatocellular carcinoma. Cancer 2005; (103) 2558– 2565.

  27. El-Houseini M, El-Sherbiny M, Awad M, et al. Serum alpha-L-fucosidase enzyme activity as a marker for hepatocellular carcinoma: comparison with AFP using ROC analysis cancer inst. 2001;(13) 277-283.

Download references

Conflicts of interest

None

Author information

Authors and Affiliations

  1. Clinical and Chemical Pathology Department, Faculty of Medicine, Cairo University, Cairo, Egypt

    Nehad A. Mossad & Enas H. Mahmoud

  2. Clinical and Chemical Pathology Department, Theodor Bilharz Research Institute (TBRI), Cairo, Egypt

    Enas A. Osman

  3. Endemic Hepatogastroenterology Department, Faculty of Medicine, Cairo University, Cairo, Egypt

    Sherif H. Mahmoud

  4. Endemic Hepatogastroenterology Department, Kasr Al-Ainy Hospital, Faculty of Medicine, Cairo University, Cairo, Egypt

    Hend I. Shousha

Authors
  1. Nehad A. Mossad
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Enas H. Mahmoud
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Enas A. Osman
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sherif H. Mahmoud
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hend I. Shousha
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hend I. Shousha.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mossad, N.A., Mahmoud, E.H., Osman, E.A. et al. Evaluation of squamous cell carcinoma antigen-immunoglobulin M complex (SCCA-IGM) and alpha-l-fucosidase (AFU) as novel diagnostic biomarkers for hepatocellular carcinoma. Tumor Biol. 35, 11559–11564 (2014). https://doi.org/10.1007/s13277-014-2467-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-014-2467-y

Keywords

Search

Navigation