Alvaro et al., (2004), Alvaro et al., (2006) found estrogen receptor alpha (RE-α) expression to be four times higher in malignant cholangiocytes than in cholangiocytes in cases of benign diseases, such as primary sclerosing cholangitis, primary biliary cirrhosis, and alcoholic cirrhosis. This evidence concerns the gene PHB2 and sclerosing cholangitis.