Advertisement

Tumor Biology

, Volume 35, Issue 11, pp 11559–11564 | Cite as

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

  • Nehad A. Mossad
  • Enas H. Mahmoud
  • Enas A. Osman
  • Sherif H. Mahmoud
  • Hend I. Shousha
Research Article

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.

Keywords

SCCA-IgM Alpha-l-fucosidase AFP Hepatocellular carcinoma 

Notes

Conflicts of interest

None

References

  1. 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.PubMedCrossRefGoogle Scholar
  2. 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.Google Scholar
  3. 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.PubMedCentralPubMedCrossRefGoogle Scholar
  4. 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.Google Scholar
  5. 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.Google Scholar
  6. 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.PubMedCrossRefGoogle Scholar
  7. 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. 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.Google Scholar
  9. 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.PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Cordero O, Ana M, Nogueira M, Vicenta S. Cell surface human alpha-L-fucosidase. Eur J Biochem. 2001;268:3321–31.PubMedCrossRefGoogle Scholar
  11. 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.PubMedCrossRefGoogle Scholar
  12. 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.CrossRefGoogle Scholar
  13. 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.Google Scholar
  14. 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.Google Scholar
  15. 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.Google Scholar
  16. 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.Google Scholar
  17. 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.Google Scholar
  18. 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.CrossRefGoogle Scholar
  19. 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.PubMedCrossRefGoogle Scholar
  20. 20.
    Bertino G, Ardiri A, Malaguarnera M, Malaguarnera G, Bertino N, Calvagno GS. Hepatocellualar carcinoma serum markers. Semin Oncol. 2012;39(4):410–33.PubMedCrossRefGoogle Scholar
  21. 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.Google Scholar
  22. 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.PubMedCentralPubMedCrossRefGoogle Scholar
  23. 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.PubMedCentralPubMedCrossRefGoogle Scholar
  24. 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. 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.Google Scholar
  26. 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.Google Scholar
  27. 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.Google Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Nehad A. Mossad
    • 1
  • Enas H. Mahmoud
    • 1
  • Enas A. Osman
    • 2
  • Sherif H. Mahmoud
    • 3
  • Hend I. Shousha
    • 4
  1. 1.Clinical and Chemical Pathology Department, Faculty of MedicineCairo UniversityCairoEgypt
  2. 2.Clinical and Chemical Pathology DepartmentTheodor Bilharz Research Institute (TBRI)CairoEgypt
  3. 3.Endemic Hepatogastroenterology Department, Faculty of MedicineCairo UniversityCairoEgypt
  4. 4.Endemic Hepatogastroenterology Department, Kasr Al-Ainy Hospital, Faculty of MedicineCairo UniversityCairoEgypt

Personalised recommendations