Serum Neopterin as a Marker for Screening of Hepatocellular Carcinoma

Abstract As Screening markers for hepatocellular Carcinoma (HCC), alpha-fetoprotein (AFP) and protein induced by an absence of vitamin K or antagonist-II (PIVKA-II) are widely used, but the sensitivity and specificity are not satisfactory enough. Neopterin is a biological marker for increased cell-mediated immunity, but has not been fully studied on HCC. To assess the clinical significance of serum neopterin as a screening marker for HCC, fifty-six HCC patients with liver cirrhosis (LC) and thirty-two LC patients without HCC as controls were studied. Serum neopterin level (n mol/L) was determined by immunoenzymatic assay. The sensitivity and specificity were analyzed by using ROC analysis. The mean level oi neopterin in HCC was significantly higher than that in LC (20.4 YS. 7.7 nmol/L, P<0.001). There was no significant relationship among serum AFP, PIVKA-II, and neopterin in HCC patients. When the cut-off value was set at 12 n mol/L, the sensitivity and specificity of neopterin was 88% and 73%, respectively. In patients with early HCC (<3cm), the detection rate of AFP, PIVKA-II, and neopterin was 35%, 35%, and 70 %, respectively. When all three markers were used, 95% of all HCC patients and 90% of early HCC patients could be detected. The detection rate of neopterin was not affected by ALT level, PLT count, liver function, angiographic pattern, histology, TNM stage, and type of tumor. These findings suggests that serum neopterin can be useful as a Screening marker for HCC and makes it possible to detect HCC at its earlier stage when used in combination with AFP or PIVKA-II.

[1]  Kenzo Kobayashi,et al.  Prospective study of early detection of hepatocellular carcinoma in patients with cirrhosis , 1990, Hepatology.

[2]  Kenichi Kobayashi,et al.  Screening methods for early detection of hepatocellular carcinoma , 1985, Hepatology.

[3]  Ding‐Shinn Chen,et al.  Serum alphafetoprotein in hepatocellular carcinoma , 1977, Cancer.

[4]  D. Fuchs,et al.  Immune response-associated production of neopterin. Release from macrophages primarily under control of interferon-gamma , 1984, The Journal of experimental medicine.

[5]  T. Maeda,et al.  Protein induced by vitamin K absence or antagonist II as a prognostic marker in hepatocellular carcinoma. Comparison with alpha‐fetoprotein , 1994, Cancer.

[6]  H. Wachter Neopterin : biochemistry, methods, clinical application , 1992 .

[7]  P. Hermanek,et al.  [TNM classification of malignant tumors: a new 1987 edition]. , 1987, Der Pathologe.

[8]  E. Werner,et al.  Neopterin modulates toxicity mediated by reactive oxygen and chloride species , 1993, FEBS letters.

[9]  G Reibnegger,et al.  Neopterin as a predictive marker for disease progression in human immunodeficiency virus type 1 infection. , 1989, Clinical chemistry.

[10]  H. Hsu,et al.  Early detection of hepatocellular carcinoma by real‐time ultrasonography. A prospective study , 1985, Cancer.

[11]  S. Fujiyama,et al.  Clinical usefulness of des-γ-carboxy prothrombin assay in early diagnosis of hepatocellular carcinoma , 1991, Digestive Diseases and Sciences.

[12]  E. Werner,et al.  POSTTRANSPLANT NEOPTERIN EXCRETION IN RENAL ALLOGRAFT RECIPIENTS—A RELIABLE DIAGNOSTIC AID FOR ACUTE REJECTION AND A PREDICTIVE MARKER OF LONG‐TERM GRAFT SURVIVAL , 1991, Transplantation.

[13]  H. Edmondson,et al.  Primary carcinoma of the liver. A study of 100 cases among 48,900 necropsies , 1954, Cancer.

[14]  R. Pugh,et al.  Transection of the oesophagus for bleeding oesophageal varices , 1973, The British journal of surgery.

[15]  G. Werner-Felmayer,et al.  Neopterin derivatives together with cyclic guanosine monophosphate induce c‐fos gene expression , 1994, FEBS letters.

[16]  D. Fuchs,et al.  Urinary neopterine excretion in patient with genital cancer. , 1982, Clinical biochemistry.

[17]  D. Fuchs,et al.  Serum soluble markers of immune activation and disease activity in systemic lupus erythematosus , 1995, Lupus.

[18]  E. Werner,et al.  Urinary neopterin reflects clinical activity in patients with rheumatoid arthritis. , 1986, Arthritis and rheumatism.

[19]  Shou-Dong Lee,et al.  Des-γ-Carboxy (Abnormal) Prothrombin as a Serum Marker of Primary Hepatocellular Carcinoma , 1984 .

[20]  M. Cottone,et al.  Early detection of hepatocellular carcinoma associated with cirrhosis by ultrasound and alfafetoprotein: a prospective study. , 1988, Hepato-gastroenterology.

[21]  G. Reibnegger,et al.  Neopterin and prognosis in patients with adenocarcinoma of the colon. , 1993, Cancer research.

[22]  E. Feller,et al.  Evidence that normal liver regeneration does not induce AFP , 1978 .

[23]  E. Werner,et al.  Enhancement of hydrogen peroxide‐induced luminol‐dependent chemiluminescence by neopterin depends on the presence of iron chelator complexes , 1994, FEBS letters.

[24]  K. Isselbacher,et al.  -fetoprotein in human hepatoma: improved detection in serum, and quantitative studies using a new sensitive technique. , 1971, Gastroenterology.

[25]  H Wachter,et al.  Neopterin as a prognostic indicator in patients with carcinoma of the uterine cervix. , 1986, Cancer research.

[26]  D. Fuchs,et al.  Neopterin is an independent prognostic variable in females with breast cancer. , 1999, Clinical chemistry.

[27]  H. Kawasaki,et al.  Prognostic significance of urinary neopterin levels in patients with hepatocellular carcinoma. , 1988, The Tohoku journal of experimental medicine.