National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines for use of tumor markers in liver, bladder, cervical, and gastric cancers.

BACKGROUND: Updated National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines for the use of tumor markers in the clinic have been developed. METHODS: Published reports relevant to use of tumor markers for 4 cancer sites--liver, bladder, cervical, and gastric--were critically reviewed. RESULTS: Alpha-fetoprotein (AFP) may be used in conjunction with abdominal ultrasound for early detection of hepatocellular carcinoma (HCC) in patients with chronic hepatitis or cirrhosis associated with hepatitis B or C virus infection. AFP concentrations >200 microg/L in cirrhotic patients with typical hypervascular lesions >2 cm in size are consistent with HCC. After a diagnosis of HCC, posttreatment monitoring with AFP is recommended as an adjunct to imaging, especially in the absence of measurable disease. Although several urine markers have been proposed for bladder cancer, none at present can replace routine cystoscopy and cytology in the management of patients with this malignancy. Some may, however, be used as complementary adjuncts to direct more effective use of clinical procedures. Although carcinoembryonic antigen and CA 19-9 have been proposed for use gastric cancer and squamous cell carcinoma antigen for use in cervical cancer, none of these markers can currently be recommended for routine clinical use. CONCLUSIONS: Implementation of these recommendations should encourage optimal use of tumor markers for patients with liver, bladder, cervical, or gastric cancers.

Differential seroprevalences of hepatitis C virus, hepatitis B virus and human immunodeficiency virus among intravenous drug users, commercial sex workers and patients with sexually transmitted diseases in Chiang Mai, Thailand.

To elucidate the differences in the mode of transmission of three blood-borne viruses, hepatitis C virus (HCV), hepatitis B virus (HBV) and human immunodeficiency virus (HIV), under comparable conditions of study, we analyzed the prevalences of anti-HCV antibodies (anti-HCV), anti-HBV core antibodies (anti-HBc), HBV surface antigen (HBsAg) and anti-HIV antibodies (anti-HIV) in different risk populations in Chiang Mai, Thailand, where the prevalence of HIV infection is high. The subjects consisted of 98 intravenous drug users (IVDU), 100 commercial sex workers (CSW) and 50 male patients with sexually transmitted diseases (STD). In IVDU the prevalence of anti-HCV was the highest (85%), followed by anti-HBc (77%) and anti-HIV (46%), whereas in CSW and STD the prevalence of anti-HCV was 2 and 0%, respectively, that of anti-HBc 69 and 64%, respectively, and that of anti-HIV 11 and 14%, respectively. The prevalence of anti-HBc minus that of HBsAg, representing horizontal transmission of HBV, was similar for IVDU (63%), CSW (58%) and STD (64%). Thus, HCV is mainly transmitted by blood contact, HIV primarily by blood contact rather than by sexual contact, and HBV equally readily by blood or sexual contact. These findings were supported by the results of logistic regression analysis.

Differential responses of serum gamma-glutamyltransferase to alcohol intake in Japanese males.

We studied the association of gamma-glutamyltransferase (GGT) and other serum markers of liver injury with daily alcohol consumption in a healthy population of 1,043 Japanese males. A positive correlation between daily alcohol consumption and biochemical markers, such as log GGT (r = 0.432), log AST (r = 0.244) or log LAP (r = 0.246), was seen in all drinkers. However, there was a negative correlation, such as log GGT (r = -0.434), log AST (r = -0.424) or log LAP (r = -0.430), in heavy drinkers who consumed more than 70 g ethanol a day. On the other hand, a positive correlation, such as log GGT (r = 0.426), log AST (r = 0.247) or log LAP (r = 0.216) was found in moderate drinkers who consumed less than 70 g ethanol a day. Interestingly, there was a tendency toward negative association between alcohol consumption and the Tokyo University ALDH2 Phenotype Screening Test (TAST) score in the heavy drinkers, and there was a tendency toward positive association between GGT and TAST score in this group. Our results suggest that there are 2 groups of drinkers, those with elevated GGT (good responders) and those with normal GGT (poor responders) despite heavy drinking.

Evaluation of tumor markers for the detection of hepatocellular carcinoma in Yangon General Hospital, Myanmar.

Levels of alpha-fetoprotein (AFP), its glycoforms AFP-L3 and AFP-P4, and proteins induced by vitamin K absence or antagonist-II (PIVKA-II) were determined in sera obtained from patients in Yangon General Hospital (20 with hepatocellular carcinoma (HCC), 29 with chronic liver diseases, including 3 with chronic hepatitis and 26 with cirrhosis of the liver, and 9 with other hepatobiliary diseases). Forty-five percent of the patients with HCC had serum AFP levels above 10,000 ng/ml, indicating that nearly half of the HCC patients were at an advanced stage of the disease. Thus, the AFP sensitivity was as high as 70% with 100% specificity for a cutoff level of 200 ng/ml. The sensitivity of AFP-L3 was 75% and a specificity 90% for a cutoff level of 15%. AFP-P4 showed a higher sensitivity of 80% and a similar specificity of 86% for a cutoff level of 12%. Combined evaluation of AFP-L3 and/or AFP-P4 increased the sensitivity to 90% with the same specificity of 86%, indicating that AFP-L3 and AFP-P4 are useful as adjuncts for diagnosis of HCC in the present population. PIVKA-II had a high sensitivity of 90%, although the specificity was lower than 45%, probably due to the low cutoff level, as some cholestatic patients were included in the control group.

Associations of serum retinol, α-tocopherol, and γ-tocopherol with biomarkers among healthy Japanese men.

Retinol, α-tocopherol, and γ-tocopherol are fat-soluble vitamins acting as antioxidants via the prevention of lipid oxidation. Little is known about circulatory levels in healthy individuals. The present cross-sectional study aimed at elucidating the relationship between these antioxidants and clinical biomarkers in 206 male (median age 41 years, range 23-67) employees from companies located in the Okayama Prefecture, Japan. Subjects younger than 40 years (n = 94) showed a positive association of the frequency of alcohol consumption with the circulating retinol (ß = 0.344, p = 0.001) and γ-tocopherol levels (ß = 0.219, p = 0.041), and an inverse association of fast insulin with serum retinol (ß = -0.301, p = 0.009). In participants older than 40 years (n = 112) we found that an inverse association of HOMA-R with serum retinol (ß = -0.262, p = 0.021), α-tocopherol (ß = -0.236, p = 0.035), and γ-tocopherol levels (ß = -0.224, p = 0.052); and cigarette smoking was inversely associated with the levels of serum α-tocopherol (ß = -0.286, p = 0.008) and γ-tocopherol (ß = -0.229, p = 0.040). We further found negative relationships between serum ferritin and the retinol (ß = -0.211, p = 0.032) and α-tocopherol levels (ß = -0.223, p = 0.022) in men over 40 years of age. The present study suggests that the circulatory levels of antioxidant vitamins may modulate the action of insulin and that higher levels of iron might decrease the levels of antioxidant vitamins in the blood.

Comparison of serum ferritin and oxidative stress biomarkers between Japanese workers with and without metabolic syndrome.

OBJECTIVE: Metabolic syndrome (MS) is closely associated to life-style and is characterized by central obesity causing severe diseases such as diabetes mellitus (DM) or atherosclerosis. This study investigates the role of oxidative stress and inflammation in MS. SUBJECTS: Total of 685 workers stratified by gender (293 men and 392 women) with a mean age of 41.2 ± 10.4 in different offices in a city in Japan. METHODS: Fasting blood and urine tests for MS, oxidative and/or inflammatory biomarker analysis and blood pressure (BP) measurement were performed. MS was defined on the basis of the Japanese criterion. RESULTS: Serum ferritin and urinary hydrogen peroxide (H2O2) levels were significantly higher in subjects with MS than those without. Ferritin was positively correlated with 8-hydroxy-2'-deoxyguanosine (8-OHdG) in all subjects and it was negatively correlated with 8-isoprostane and H2O2 in men. In addition, there was a significant positive correlation between ferritin and homeostasis model assessment (HOMA-R) in men. By using multiple regression analysis, ferritin was closely correlated with HOMA-R, γ-GT, 8-OHdG, smoking value and amount of alcohol ingestion in men, and it was correlated with 8-OHdG, γ-GT, HOMA-R in women under 50 years old. CONCLUSIONS: Ferritin is a useful marker of MS including insulin resistance, reflecting the importance of oxidative stress as a cause of MS, especially in men.

Further resolution of alpha-fetoprotein glycoforms by two-dimensional isoelectric focusing and lectin affinity electrophoresis.

Human alpha-fetoprotein (AFP) from serum of patients with cirrhosis and hepatocellular carcinoma (HCC) was separated into several bands by IEF and by erythroagglutinating phytohemagglutinin (E-PHA) affinity electrophoresis. These AFP bands were directly compared in 2-D IEF and E-PHA affinity electrophoresis. IEF of serum AFP was run in 1% agarose IEF gel with 3% Pharmalyte 4.5-5.4. After IEF, a part of the gel was stained for AFP and another part of the gel corresponding to the area of separated AFP bands was cut in 1 mm x 39 mm along the focused direction and transferred to a trough in 1% agarose gel with 0.3 mg/mL E(4)-PHA for second-dimensional affinity electrophoresis. Separated 2-D AFP spots were visualized by antibody-affinity blotting and identified by combining the systems of Johnson et al.. (Johnson, P. J., Ho, S., Cheng, P., Chan, A. et al.., Cancer 1995, 75, 1663-1668) for AFP-I-+IV and of Taketa et al.. (Taketa, K., Ichikawa, E., Taga, H., Hirai, H., Electrophoresis 1985, 6, 492-497) for AFP-P1-5. AFP-P2, the major AFP glycoform, was composed of AFP-I, AFP+I, and AFP+II; AFP-P3, a nonspecific monosialo-AFP, was composed of AFP+II; AFP-P4, HCC-specific monosialo-AFP, was composed of AFP+II, AFP+III, and AFP+IV; and malignancy-related AFP-P5 was composed of AFP+I and AFP+II. Monosialo-AFP (AFP+II) was recovered in all the glycoforms of AFP-P2, -P3, -P4, and -P5; thus, AFP-P4 is more specific to HCC than monosialylated AFP+II.

High level of expression of alpha-fetoprotein receptor in gastric cancers.

The expression of the receptor for alpha-fetoprotein (AFP-R) was examined immunohistochemically in 47 cancer and 14 benign human gastric tissues. Rabbit polyclonal antibody against human AFP-R was used for immunohistochemical staining. Thirty-four of the 47 cancer tissues expressed AFP-R showing granular or reticular staining on the cancer cell surface, while only 2 of 61 control cases (14 benign gastric tissues and 47 nonmalignant tissues adjacent to cancer) showed faint and homogeneous staining in the cytoplasm of noncancerous cells. There was a significant difference in staining intensity between the cancerous and noncancerous groups. However, no statistically significant difference in staining intensity was found among the groups of well-differentiated, moderately differentiated and poorly differentiated adenocarcinomas. On the other hand, the staining intensity of signet ring cell carcinoma was significantly weaker than that of the three adenocarcinoma groups. The high level of AFP-R expression in gastric cancers may allow the use of AFP-R as a new clinically useful marker of gastric cancer in the tissue level.

Hemoglobinopathies, Iron Overload and Chronic Viral Hepatitis in Patients with Hepatocellular Carcinoma in Myanmar.

To assess the relevance of altered iron metabolism, hemoglobin electrophoresis by isoelectric focusing was performed for 16 cases of hepatocellular carcinoma (HCC) from the Liver Unit, Yangon General Hospital. Serum iron, total iron binding capacity, serum ferritin and free iron were also determined. Hemoglobin A (HbA) was found in all of the cases. Four cases had one extra band, hemoglobin A(2) in three cases, and hemoglobin F in one case. No abnormal hemoglobin was detected. Anemias due to chronic disorders or associated with liver disease were observed in all of the cases. Iron overload was documented in 83% and free iron was detected in all cases. Viral markers like HBsAg, AntiHBc, and AntiHCV singly or in combination were found in all cases. HCC occurring at young age was seen in this study; the youngest patient was 23 years old and four cases (25%) were under 40 years, with a mean age of 49 years. The findings support the hypothesis that free iron and iron overload is a potential promoter of the development of HCC, especially if underlying chronic viral infection is present.