BACKGROUND.Early detection of hepatocellular carcinoma (HCC), one of the most common and deadly tumors worldwide, still is difficult due to the lack of adequate biomarkers that show high sensitivity and specificity. The authors recently demonstrated that squamous cell carcinoma antigen (SCCA) variants were overexpressed remarkably in all surgically resected HCCs. METHODS.For the current study, the authors assessed the presence of SCCA, as a free form and complexed with immunoglobulins, in serum from patients with HCC, cirrhosis, and chronic hepatitis and from healthy control participants and compared SCCA measurement with the measurement of ␣-fetoprotein (AFP) levels. RESULTS.Circulating immune complexes (ICs) composed by SCCA and immunoglobulin M (IgM) IC (SCCA-IgM IC) were undetectable (Ͻ 120 arbitrary units[AU]/mL) in serum from a healthy control population (0 of 73 controls); however, 35 of 50 patients with HCC (70%) were reactive for SCCA-IgM IC independent of etiology (mean Ϯ standard deviation [SD], 2568.5 Ϯ 6797.3 AU/mL). No correlation was found with AFP levels, which were elevated significantly in only 21 of 50 patients with HCC (42%). By using an AFP cut-off value of 20 ng/mL, 96% of patients with HCC were positive for at least 1 marker. Among cirrhotic patients, the presence of circulating SCCA-IgM IC was displayed in 13 of 50 patients (26%), but at lower levels compared with the patients who had HCC (mean Ϯ SD, 147.5 Ϯ 348.3 AU/mL; P Ͻ 0.01; Student t test), whereas 9 of 50 patients with chronic hepatitis (18%) were reactive (mean Ϯ SD, 39.5 Ϯ 89.7 AU/mL). No significant presence of free SCCA, free anti-SCCA variants IgG or IgM, or SCCA-IgG IC was found. CONCLUSIONS.The study results indicated that SCCA-IgM ICs represent novel serologic biomarkers, which, alone or in combination with AFP, can increase the sensitivity for diagnosing HCC significantly.

We sought a correlation between rat skeletal muscle triiodothyronine (T3)-mediated regulation of uncoupling protein-3 (UCP3) expression and mitochondrial activity. UCP3 mRNA expression increased strongly during the hypothyroid-hyperthyroid transition. The rank order of mitochondrial State 3 and State 4 respiration rates was hypothyroid 6 euthyroid 6 hyperthyroid. The State 4 increase may have been due to the increased UCP3 expression, as the proton leak kinetic was stimulated in the hypothyroid-hyperthyroid transition and a good correlation exists between the State 4 and UCP3 mRNA level. As a significant proportion of an organism's resting oxygen consumption is dedicated to opposing the proton leak, skeletal muscle mitochondrial UCP3 may mediate part of T3's effect on energy metabolism.z 1999 Federation of European Biochemical Societies.

About 3-4% of cirrhotic patients develop primary liver cancer every year. Specific serologic markers have not yet been identified for screening of high risk patients. The serpin squamous cell carcinoma antigen (SCCA) is overexpressed in liver cancer and circulating SCCA-IgM complexes have been described in patients with hepatocellular carcinoma (HCC). The aim of the present study was to assess the behavior of SCCA-IgM in relation to HCC development in patients with cirrhosis. A retrospective, longitudinal study was conducted in a cohort of prospectively followed cirrhotic patients. Two groups with similar clinical profile at presentation were studied : group A included 16 patients who developed HCC during a median follow up of 4 years; group B included 17 patients who did not develop HCC during the same time interval. Circulating SCCA-IgM immune complexes were determined using a recently standardized ELISA assay. At presentation similar levels of SCCA-IgM complexes [mean 6 SD: 267.40 6 382.25 U/ml vs. 249.10 6 446.90 U/ml, p 5 0.9006] and of alpha-fetoprotein [AFP; 24.11 6 59.04 IU/ml vs. 10.91 6 23.34 IU/ml, p 5 0.3995] were detected in group A and in group B. The increase over time (/) of SCCA-IgM, assessed within at least one year before clinical diagnosis of HCC, was remarkably higher in group A than in group B (mean 6 SD 5 280.05 6 606.71 (U/ml)/year vs. 237.92 6 95.94 (U/ml)/year, p 5 0.0408), while AFP increase was not significantly different (11.89 6 23.27 (IU/ml)/year vs. 3.67 6 11.46 (IU/ ml)/year, p 5 0.2179). Receiver operating characteristic (ROC) curves were plotted for the rate of change in the levels of both markers and the diagnostic accuracy measured as AUROC was higher for SCCA-IgM / (0.821) than for AFP / (0.654). In conclusion, the progressive increase of SCCA-IgM over time was associated with liver tumor development, suggesting that monitoring the behavior of SCCA-IgM might become useful to identify cirrhotic patients at higher risk of HCC development. ' 2006 Wiley-Liss, Inc.Key words: SCCA-IgM; hepatocellular carcinoma; serologic prognostic marker; cirrhosis Hepatocellular carcinoma (HCC) is one of the major health problems worldwide, due to its high incidence and severe prognosis. Figures depicting half a million new cases per year have been reported, and projection studies have estimated an increase of tumor development within the next decade in developed countries. 1The reasons advocated to explain this phenomenon are the increased rate of HCV infection and an improvement in clinical management of liver cirrhosis, identified as the major risk factor for HCC development.2 About 3-4% of cirrhotic patients develop primary liver cancer every year and this justifies surveillance programs to detect HCC at an early stage. 3 The prognosis of the patients depends mainly on the evolutionary stage of the neoplasm, ranging from 5-years survival higher than 70% in surgical patients to less than 3 months in very advanced tumors. 4 Tumor size is one of the main factors influencing the possibility of b...

About 30% of the patients with chronic hepatitis develop a progressive liver disease and one of the most intriguing issues is the detection of noninvasive markers for fibrosis stage and disease progression. High levels of squamous cell carcinoma antigen (SCCA)-immunoglobulin M (IgM) are detectable in hepatocellular carcinoma and their increase in cirrhotic patients can predict tumour development. As SCCA-IgM can also be detectable at low percentages in patients with chronic hepatitis, the aim of this study was to assess SCCA-IgM complexes in relation to disease outcome in this group of patients. An ELISA assay was used to determine the presence of SCCA-IgM in 188 patients with chronic hepatitis and in 100 controls. An additional serum sample was available after a median period of 6 years in 57 untreated patients: these patients were subdivided in group A, including eight patients with a fibrosis score increase > or =2 in a second liver biopsy and group B, including 49 patients without fibrosis progression during a similar follow up. SCCA-IgM complexes were detectable in 63 of 188 (33%) patients but in none of the controls. A significant increase of SCCA-IgM levels over time was observed in patients with fibrosis progression (mean +/- SD: 117 +/- 200 U/mL/year), but not in those without histologic deterioration (mean +/- SD: -8.8 +/- 31 U/mL/year, P < 0.0001). In conclusion, monitoring SCCA-IgM levels over time appears a useful approach to identify patients with chronic hepatitis at higher risk for cirrhosis development.

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