FAT, E-cadherin, β catenin, HER 2/neu, Ki67 immunoexpression, and histological grade in intrahepatic cholangiocarcinoma

Aim: To identify surrogate prognostic markers in intrahepatic cholangiocarcinoma (IHCC). Methods: Thirty one cases of IHCC were graded and immunostained for FAT, Ki67, E-cadherin, β catenin, and HER 2/neu. Results: Twenty two cases were high grade and 27 had high Ki67 counts. Strong membranous staining of HER 2/neu was found in 10 tumours and reduced membranous E-cadherin and β catenin in 19 and 18 tumours, respectively. Nuclear localisation of β catenin was identified in five tumours and 22 showed weak cytoplasmic staining of FAT. Strong HER 2/neu and weak FAT immunoexpression were significantly correlated with high histological grade (p  =  0.01) and high Ki67 index (p  =  0.03). Upregulation of HER 2/neu was also significantly associated with nuclear localisation of β catenin (p  =  0.01). Reduced membranous β catenin was significantly related to reduced membranous E-cadherin (p  =  0.03), weak staining for FAT (p  =  0.01), and nuclear translocation of β catenin (p  =  0.04). Conclusions: Reduced immunoexpression of E-cadherin and FAT at their normal membranous location may be potential prognostic markers, and the overexpression of HER 2/neu and β catenin nuclear translocation may have a role in cholangiocarcinogenesis

Protective roles of ascorbic acid in oxidative stress induced by depletion of superoxide dismutase in vertebrate cells

Superoxide dismutases (SODs) are antioxidant proteins that convert superoxide to hydrogen peroxide. In vertebrate cells, SOD1 is mainly present in the cytoplasm, with small levels also found in the nucleus and mitochondrial intermembrane space, and SOD2 is present in the mitochondrial matrix. Previously, the authors conditionally disrupted the SOD1 or SOD2 gene in DT40 cells and found that depletion of SOD1 caused lethality, while depletion of SOD2 led to growth retardation. The observations from previous work showed that the lethality observed in SOD1-depleted cells was completely rescued by ascorbic acid. Ascorbic acid is a water-soluble antioxidant present in biological fluids; however, the exact target for its antioxidant effects is not known. In this study, the authors demonstrated that ascorbic acid offset growth defects observed in SOD2-depleted cells and also lowered mitochondrial superoxide to physiological levels in both SOD1- or SOD2-depleted cells. Moreover, depletion of SOD1 or SOD2 resulted in the accumulation of intracellular oxidative stress, and this increased oxidative stress was reduced by ascorbic acid. Taken together, this study suggests that ascorbic acid can be applied as a nontoxic antioxidant that mimics the functions of cytoplasmic and mitochondrial SODs