Skip to main content
Erschienen in: Journal of Gastrointestinal Cancer 3/2019

06.04.2018 | Original Research

Significance of Glypican-3 in Early Detection of Hepatocellular Carcinoma in Cirrhotic Patients

verfasst von: Ahmed M. Tahon, Magdy Z. El-Ghanam, Samy Zaky, Tarek Mostafa Emran, Ali M. Bersy, Fathiya El-Raey, Elsayed A.Z., Amr M. El Kharsawy, Dina Johar

Erschienen in: Journal of Gastrointestinal Cancer | Ausgabe 3/2019

Einloggen, um Zugang zu erhalten

Abstract

Background

Egypt has high incidence of hepatocellular carcinoma (HCC). This is due to wide spread of hepatitis C virus (HCV) infection which is responsible for most of the cases of liver cirrhosis. The major diagnostic techniques for HCC include serum markers and various imaging modalities. Glypican 3 (GPC3) protein is highly expressed in HCC, but not in normal liver tissue. The significance of GPC3 as a predictor or diagnostic tool for human tumors other than HCC is unclear.

Aim

To quantitatively assess the role of GPC3 in diagnosis of HCC in comparison to α-fetoprotein (AFP), ultrasonography (US), and computerized tomography (CT).

Patients and Methods

This cross-sectional study enrolled 85 subjects: 40 cirrhotic patients with primary HCC, 30 cirrhotic patients without HCC, and 15 healthy individuals. All patients were recruited from the Gastroenterology and Tropical Departments and outpatient clinics of New Damietta Hospital during the period from November 2010 to August 2012.

Results

GPC3 is positive in some HCC patients with normal levels of AFP. AFP has lower sensitivity (67.5%) compared to higher sensitivity of GPC3 (82.5%), and near specificity (61.2%) to GPC3 (57.8%).

Conclusion and Significance

The combined serum AFP and GPC3 significantly increased the sensitivity of HCC diagnosis. Although GPC3 is better than AFP in diagnosis of HCC, it still lacks the 100% sensitivity and specificity because some patients have negative or normal level of GPC3 (below the cutoff point 1.5 ng/ml) despite being diagnosed by triphasic CT.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Siegel R, Naishadham D, Jemal A. Cancer statistics for Hispanics/Latinos, 2012. CA Cancer J Clin. 2012;62(5):283–98.CrossRef Siegel R, Naishadham D, Jemal A. Cancer statistics for Hispanics/Latinos, 2012. CA Cancer J Clin. 2012;62(5):283–98.CrossRef
2.
Zurück zum Zitat Stefaniuk P, Cianciara J, Wiercinska-Drapalo A. Present and future possibilities for early diagnosis of hepatocellular carcinoma. World J Gastroenterol. 2010;16(4):418–24.CrossRef Stefaniuk P, Cianciara J, Wiercinska-Drapalo A. Present and future possibilities for early diagnosis of hepatocellular carcinoma. World J Gastroenterol. 2010;16(4):418–24.CrossRef
3.
Zurück zum Zitat Wang FH, Yip YC, Zhang M, Vong HT, Chan KI, Wai KC, et al. Diagnostic utility of glypican-3 for hepatocellular carcinoma on liver needle biopsy. J Clin Pathol. 2010;63(7):599–603.CrossRef Wang FH, Yip YC, Zhang M, Vong HT, Chan KI, Wai KC, et al. Diagnostic utility of glypican-3 for hepatocellular carcinoma on liver needle biopsy. J Clin Pathol. 2010;63(7):599–603.CrossRef
4.
Zurück zum Zitat Liu Y, Wu F. Global burden of aflatoxin-induced hepatocellular carcinoma: a risk assessment. Environ Health Perspect. 2010;118(6):818–24.CrossRef Liu Y, Wu F. Global burden of aflatoxin-induced hepatocellular carcinoma: a risk assessment. Environ Health Perspect. 2010;118(6):818–24.CrossRef
5.
Zurück zum Zitat Nakatsura T, Yoshitake Y, Senju S, Monji M, Komori H, Motomura Y, et al. Glypican-3, overexpressed specifically in human hepatocellular carcinoma, is a novel tumor marker. Biochem Biophys Res Commun. 2003;306(1):16–25.CrossRef Nakatsura T, Yoshitake Y, Senju S, Monji M, Komori H, Motomura Y, et al. Glypican-3, overexpressed specifically in human hepatocellular carcinoma, is a novel tumor marker. Biochem Biophys Res Commun. 2003;306(1):16–25.CrossRef
6.
Zurück zum Zitat Allegretta M, Filmus J. Therapeutic potential of targeting glypican-3 in hepatocellular carcinoma. Anti Cancer Agents Med Chem. 2011;11(6):543–8.CrossRef Allegretta M, Filmus J. Therapeutic potential of targeting glypican-3 in hepatocellular carcinoma. Anti Cancer Agents Med Chem. 2011;11(6):543–8.CrossRef
7.
Zurück zum Zitat Ho M, Kim H. Glypican-3: a new target for cancer immunotherapy. Eur J Cancer. 2011;47(3):333–8.CrossRef Ho M, Kim H. Glypican-3: a new target for cancer immunotherapy. Eur J Cancer. 2011;47(3):333–8.CrossRef
8.
Zurück zum Zitat Hameed MA, Waqas S. Physiological basis and clinical utility of erythrocyte sedimentation rate. Continuing Med Educ. 2006;22(2) Hameed MA, Waqas S. Physiological basis and clinical utility of erythrocyte sedimentation rate. Continuing Med Educ. 2006;22(2)
9.
Zurück zum Zitat Amatuzio DS, Grande F, Wada S. The cyanmethemoglobin method for hemoglobin determination. Minn Med. 1962;45:378–81.PubMed Amatuzio DS, Grande F, Wada S. The cyanmethemoglobin method for hemoglobin determination. Minn Med. 1962;45:378–81.PubMed
10.
Zurück zum Zitat Lewis S, Barbara B, Imelda B. Dacie and Lewis Practical Haematology, 10th Edition. Churchill Livingstone. 2006. Lewis S, Barbara B, Imelda B. Dacie and Lewis Practical Haematology, 10th Edition. Churchill Livingstone. 2006.
11.
Zurück zum Zitat Grant GH, Kachmar JF. Fundamentals of clinical chemistry. Tietz NW, ed. W.B. Philadelphia: Sunders Co; 1976. Grant GH, Kachmar JF. Fundamentals of clinical chemistry. Tietz NW, ed. W.B. Philadelphia: Sunders Co; 1976.
12.
Zurück zum Zitat Webster AJ. Clearance by the hepatic portal circulation of the products of digestion and metabolism in the ruminant gut. Proc Nutr Soc. 1974;33(2):155–61.CrossRef Webster AJ. Clearance by the hepatic portal circulation of the products of digestion and metabolism in the ruminant gut. Proc Nutr Soc. 1974;33(2):155–61.CrossRef
13.
Zurück zum Zitat Bergmeyer HU, Scheibe P, Wahlefeld AW. Optimization of methods for aspartate aminotransferase and alanine aminotransferase. Clin Chem. 1978;24(1):58–73.PubMed Bergmeyer HU, Scheibe P, Wahlefeld AW. Optimization of methods for aspartate aminotransferase and alanine aminotransferase. Clin Chem. 1978;24(1):58–73.PubMed
14.
Zurück zum Zitat Tietz NW, editor. Clinical guide to laboratory tests. 3rd ed. Philadelphia: W.B. Saunders; 1995. Tietz NW, editor. Clinical guide to laboratory tests. 3rd ed. Philadelphia: W.B. Saunders; 1995.
15.
Zurück zum Zitat Lum G, Gambino SR. Serum gamma-glutamyl transpeptidase activity as an indicator of disease of liver, pancreas, or bone. Clin Chem. 1972;18(4):358–62.PubMed Lum G, Gambino SR. Serum gamma-glutamyl transpeptidase activity as an indicator of disease of liver, pancreas, or bone. Clin Chem. 1972;18(4):358–62.PubMed
16.
Zurück zum Zitat Taylor EH. Clin Chem. 1989;4:58–62. Taylor EH. Clin Chem. 1989;4:58–62.
17.
Zurück zum Zitat Traynor J, Mactier R, Geddes CC, Fox JG. How to measure renal function in clinical practice. Br Med J. 2006;333(7571):733–7.CrossRef Traynor J, Mactier R, Geddes CC, Fox JG. How to measure renal function in clinical practice. Br Med J. 2006;333(7571):733–7.CrossRef
18.
Zurück zum Zitat Lerner KK, Lerner BW. World of microbiology and immunology. Volumes 1 and 2. Andover: Cengage Gale Publisher; 2003. p. 231–232. Lerner KK, Lerner BW. World of microbiology and immunology. Volumes 1 and 2. Andover: Cengage Gale Publisher; 2003. p. 231–232.
19.
Zurück zum Zitat Libbrecht L, Severi T, Cassiman D, Vander Borght S, Pirenne J, Nevens F, et al. Glypican-3 expression distinguishes small hepatocellular carcinomas from cirrhosis, dysplastic nodules, and focal nodular hyperplasia-like nodules. Am J Surg Pathol. 2006;30(11):1405–11.CrossRef Libbrecht L, Severi T, Cassiman D, Vander Borght S, Pirenne J, Nevens F, et al. Glypican-3 expression distinguishes small hepatocellular carcinomas from cirrhosis, dysplastic nodules, and focal nodular hyperplasia-like nodules. Am J Surg Pathol. 2006;30(11):1405–11.CrossRef
20.
Zurück zum Zitat Gurakar A, Hamilton J, Koteish A. Diagnosis of hepatocellular carcinoma. World J Gastroenterol. 2011;14(13):1461. Gurakar A, Hamilton J, Koteish A. Diagnosis of hepatocellular carcinoma. World J Gastroenterol. 2011;14(13):1461.
21.
Zurück zum Zitat Sung YK, Hwang SY, Park MK, Farooq M, Han IS, Bae HI, et al. Glypican-3 is overexpressed in human hepatocellular carcinoma. Cancer Sci. 2003;94(3):259–62.CrossRef Sung YK, Hwang SY, Park MK, Farooq M, Han IS, Bae HI, et al. Glypican-3 is overexpressed in human hepatocellular carcinoma. Cancer Sci. 2003;94(3):259–62.CrossRef
22.
Zurück zum Zitat Capurro M, Wanless IR, Sherman M, Deboer G, Shi W, Miyoshi E, et al. Glypican-3: a novel serum and histochemical marker for hepatocellular carcinoma. Gastroenterology. 2003;125(1):89–97.CrossRef Capurro M, Wanless IR, Sherman M, Deboer G, Shi W, Miyoshi E, et al. Glypican-3: a novel serum and histochemical marker for hepatocellular carcinoma. Gastroenterology. 2003;125(1):89–97.CrossRef
23.
Zurück zum Zitat Hippo Y, Watanabe K, Watanabe A, Midorikawa Y, Yamamoto S, Ihara S, et al. Identification of soluble NH2-terminal fragment of glypican-3 as a serological marker for early-stage hepatocellular carcinoma. Cancer Res. 2004;64(7):2418–23.CrossRef Hippo Y, Watanabe K, Watanabe A, Midorikawa Y, Yamamoto S, Ihara S, et al. Identification of soluble NH2-terminal fragment of glypican-3 as a serological marker for early-stage hepatocellular carcinoma. Cancer Res. 2004;64(7):2418–23.CrossRef
24.
Zurück zum Zitat Lu MD, Xu HX, Xie XY, Yin XY, Chen JW, Kuang M, et al. Percutaneous microwave and radiofrequency ablation for hepatocellular carcinoma: a retrospective comparative study. J Gastroenterol. 2005;40(11):1054–60.CrossRef Lu MD, Xu HX, Xie XY, Yin XY, Chen JW, Kuang M, et al. Percutaneous microwave and radiofrequency ablation for hepatocellular carcinoma: a retrospective comparative study. J Gastroenterol. 2005;40(11):1054–60.CrossRef
25.
Zurück zum Zitat Wang CS, Lin CL, Lee HC, Chen KY, Chiang MF, Chen HS, et al. Usefulness of serum des-gamma-carboxy prothrombin in detection of hepatocellular carcinoma. World J Gastroenterol. 2005;11(39):6115–9.CrossRef Wang CS, Lin CL, Lee HC, Chen KY, Chiang MF, Chen HS, et al. Usefulness of serum des-gamma-carboxy prothrombin in detection of hepatocellular carcinoma. World J Gastroenterol. 2005;11(39):6115–9.CrossRef
26.
Zurück zum Zitat El-Zayadi AR, Abaza H, Shawky S, Mohamed MK, Selim OE, Badran HM. Prevalence and epidemiological features of hepatocellular carcinoma in Egypt—a single center experience. Hepatol Res. 2001;19(2):170–9.CrossRef El-Zayadi AR, Abaza H, Shawky S, Mohamed MK, Selim OE, Badran HM. Prevalence and epidemiological features of hepatocellular carcinoma in Egypt—a single center experience. Hepatol Res. 2001;19(2):170–9.CrossRef
27.
Zurück zum Zitat Bolondi L, Piscaglia F, Camaggi V, Grazi GL, Cavallari A. Review article: liver transplantation for HCC. Treatment options on the waiting list. Aliment Pharmacol Ther. 2003;17 Suppl 2(s2):145–50.CrossRef Bolondi L, Piscaglia F, Camaggi V, Grazi GL, Cavallari A. Review article: liver transplantation for HCC. Treatment options on the waiting list. Aliment Pharmacol Ther. 2003;17 Suppl 2(s2):145–50.CrossRef
28.
Zurück zum Zitat Omata M, Lesmana LA, Tateishi R, Chen PJ, Lin SM, Yoshida H, et al. Asian Pacific Association for the Study of the liver consensus recommendations on hepatocellular carcinoma. Hepatol Int. 2010;4(2):439–74.CrossRef Omata M, Lesmana LA, Tateishi R, Chen PJ, Lin SM, Yoshida H, et al. Asian Pacific Association for the Study of the liver consensus recommendations on hepatocellular carcinoma. Hepatol Int. 2010;4(2):439–74.CrossRef
29.
Zurück zum Zitat Rodriguez-Diaz JL, Rosas-Camargo V, Vega-Vega O, Morales-Espinosa D, Mendez-Reguera A, Martinez-Tlahuel JL, et al. Clinical and pathological factors associated with the development of hepatocellular carcinoma in patients with hepatitis virus-related cirrhosis: a long-term follow-up study. Clin Oncol (R Coll Radiol). 2007;19(3):197–203.CrossRef Rodriguez-Diaz JL, Rosas-Camargo V, Vega-Vega O, Morales-Espinosa D, Mendez-Reguera A, Martinez-Tlahuel JL, et al. Clinical and pathological factors associated with the development of hepatocellular carcinoma in patients with hepatitis virus-related cirrhosis: a long-term follow-up study. Clin Oncol (R Coll Radiol). 2007;19(3):197–203.CrossRef
30.
Zurück zum Zitat Johnson P. Malignant tumors of the liver. In: O’Grady J, Lake J, editors. “Comprehensive Clinical Hepatology”. London: Haecourt; 2000. p. 25.1–25.18. Johnson P. Malignant tumors of the liver. In: O’Grady J, Lake J, editors. “Comprehensive Clinical Hepatology”. London: Haecourt; 2000. p. 25.1–25.18.
31.
Zurück zum Zitat El-Serag HB. Hepatocellular carcinoma: an epidemiologic view. J Clin Gastroenterol. 2002;35(5 Suppl 2):S72–8.CrossRef El-Serag HB. Hepatocellular carcinoma: an epidemiologic view. J Clin Gastroenterol. 2002;35(5 Suppl 2):S72–8.CrossRef
32.
Zurück zum Zitat Yu SC, Yeung DT, So NM. Imaging features of hepatocellular carcinoma. Clin Radiol. 2004;59(2):145–56.CrossRef Yu SC, Yeung DT, So NM. Imaging features of hepatocellular carcinoma. Clin Radiol. 2004;59(2):145–56.CrossRef
33.
Zurück zum Zitat el-Zayadi AR, Badran HM, Barakat EM, Attia Mel D, Shawky S, Mohamed MK, et al. Hepatocellular carcinoma in Egypt: a single center study over a decade. World J Gastroenterol. 2005;11(33):5193–8.PubMedPubMedCentral el-Zayadi AR, Badran HM, Barakat EM, Attia Mel D, Shawky S, Mohamed MK, et al. Hepatocellular carcinoma in Egypt: a single center study over a decade. World J Gastroenterol. 2005;11(33):5193–8.PubMedPubMedCentral
34.
Zurück zum Zitat Abdel-Wahab M, El-Ghawalby N, Mostafa M, Sultan A, El-Sadany M, Fathy O, et al. Epidemiology of hepatocellular carcinoma in lower Egypt, Mansoura Gastroenterology Center. Hepato-Gastroenterology. 2006;54(73):157–62. Abdel-Wahab M, El-Ghawalby N, Mostafa M, Sultan A, El-Sadany M, Fathy O, et al. Epidemiology of hepatocellular carcinoma in lower Egypt, Mansoura Gastroenterology Center. Hepato-Gastroenterology. 2006;54(73):157–62.
35.
Zurück zum Zitat Brechot C, Kremsdorf D, Soussan P, Pineau P, Dejean A, Paterlini-Brechot P, et al. Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC): molecular mechanisms and novel paradigms. Pathol Biol (Paris). 2010;58(4):278–87.CrossRef Brechot C, Kremsdorf D, Soussan P, Pineau P, Dejean A, Paterlini-Brechot P, et al. Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC): molecular mechanisms and novel paradigms. Pathol Biol (Paris). 2010;58(4):278–87.CrossRef
36.
Zurück zum Zitat Strickland GT. Liver disease in Egypt: hepatitis C superseded schistosomiasis as a result of iatrogenic and biological factors. Hepatology. 2006;43(5):915–22.CrossRef Strickland GT. Liver disease in Egypt: hepatitis C superseded schistosomiasis as a result of iatrogenic and biological factors. Hepatology. 2006;43(5):915–22.CrossRef
37.
Zurück zum Zitat Chritsopher J, Smith M. Clinician guide to viral hepatitis. Hepatol Res. 2004;32:245–61. Chritsopher J, Smith M. Clinician guide to viral hepatitis. Hepatol Res. 2004;32:245–61.
38.
Zurück zum Zitat Saini N, Bhagat A, Sharma S, Duseja A, Chawla Y. Evaluation of clinical and biochemical parameters in hepatocellular carcinoma: experience from an Indian center. Clin Chim Acta. 2006;371(1–2):183–6.CrossRef Saini N, Bhagat A, Sharma S, Duseja A, Chawla Y. Evaluation of clinical and biochemical parameters in hepatocellular carcinoma: experience from an Indian center. Clin Chim Acta. 2006;371(1–2):183–6.CrossRef
39.
Zurück zum Zitat Gad A, Tanaka E, Matsumoto A, Abd-el Wahab M, Serwah A, Attia F, et al. Assessment of KL-6 as a tumor marker in patients with hepatocellular carcinoma. World J Gastroenterol: WJG. 2005;11(42):6607–12.CrossRef Gad A, Tanaka E, Matsumoto A, Abd-el Wahab M, Serwah A, Attia F, et al. Assessment of KL-6 as a tumor marker in patients with hepatocellular carcinoma. World J Gastroenterol: WJG. 2005;11(42):6607–12.CrossRef
40.
Zurück zum Zitat Suzuki M, Shiraha H, Fujikawa T, Takaoka N, Ueda N, Nakanishi Y, et al. Des-γ-carboxy prothrombin is a potential autologous growth factor for hepatocellular carcinoma. J Biol Chem. 2005;280(8):6409–15.CrossRef Suzuki M, Shiraha H, Fujikawa T, Takaoka N, Ueda N, Nakanishi Y, et al. Des-γ-carboxy prothrombin is a potential autologous growth factor for hepatocellular carcinoma. J Biol Chem. 2005;280(8):6409–15.CrossRef
41.
Zurück zum Zitat Barletta E, Tinessa V, Daniele B. Screening of hepatocellular carcinoma: role of the alpha-fetoprotein (AFP) and ultrasonography. Recenti Prog Med. 2005;96(6):295–9. quiz 328PubMed Barletta E, Tinessa V, Daniele B. Screening of hepatocellular carcinoma: role of the alpha-fetoprotein (AFP) and ultrasonography. Recenti Prog Med. 2005;96(6):295–9. quiz 328PubMed
42.
Zurück zum Zitat Zhou L, Liu J, Luo F. Serum tumor markers for detection of hepatocellular carcinoma. World J Gastroenterol. 2006;12(8):1175–81.CrossRef Zhou L, Liu J, Luo F. Serum tumor markers for detection of hepatocellular carcinoma. World J Gastroenterol. 2006;12(8):1175–81.CrossRef
43.
Zurück zum Zitat Chen T, Huang P, Tsai M, Lin L, Liu C, Ho K, et al. Predictors of alpha-fetoprotein elevation in patients with chronic hepatitis C, but not hepatocellular carcinoma, and its normalization after pegylated interferon alfa 2a–ribavirin combination therapy. J Gastroenterol Hepatol. 2007;22(5):669–75.CrossRef Chen T, Huang P, Tsai M, Lin L, Liu C, Ho K, et al. Predictors of alpha-fetoprotein elevation in patients with chronic hepatitis C, but not hepatocellular carcinoma, and its normalization after pegylated interferon alfa 2a–ribavirin combination therapy. J Gastroenterol Hepatol. 2007;22(5):669–75.CrossRef
44.
Zurück zum Zitat Shirabe K, Itoh S, Yoshizumi T, Soejima Y, Taketomi A, Aishima S, et al. The predictors of microvascular invasion in candidates for liver transplantation with hepatocellular carcinoma-with special reference to the serum levels of des-gamma-carboxy prothrombin. J Surg Oncol. 2007;95(3):235–40.CrossRef Shirabe K, Itoh S, Yoshizumi T, Soejima Y, Taketomi A, Aishima S, et al. The predictors of microvascular invasion in candidates for liver transplantation with hepatocellular carcinoma-with special reference to the serum levels of des-gamma-carboxy prothrombin. J Surg Oncol. 2007;95(3):235–40.CrossRef
45.
Zurück zum Zitat Bongiovanni M, Ranieri R, Tincati C, Casana M, Marchetti G, Monforte A. Serum alpha-fetoprotein levels predict early virologic response in HIV-positive subjects treated for chronic hepatitis C. J Acquir Immune Defic Syndr. 2008;48(3):361–3.CrossRef Bongiovanni M, Ranieri R, Tincati C, Casana M, Marchetti G, Monforte A. Serum alpha-fetoprotein levels predict early virologic response in HIV-positive subjects treated for chronic hepatitis C. J Acquir Immune Defic Syndr. 2008;48(3):361–3.CrossRef
Metadaten
Titel
Significance of Glypican-3 in Early Detection of Hepatocellular Carcinoma in Cirrhotic Patients
verfasst von
Ahmed M. Tahon
Magdy Z. El-Ghanam
Samy Zaky
Tarek Mostafa Emran
Ali M. Bersy
Fathiya El-Raey
Elsayed A.Z.
Amr M. El Kharsawy
Dina Johar
Publikationsdatum
06.04.2018
Verlag
Springer US
Erschienen in
Journal of Gastrointestinal Cancer / Ausgabe 3/2019
Print ISSN: 1941-6628
Elektronische ISSN: 1941-6636
DOI
https://doi.org/10.1007/s12029-018-0095-2

Weitere Artikel der Ausgabe 3/2019

Journal of Gastrointestinal Cancer 3/2019 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.