The clinical and pathogenetic significance of estrogen receptor-beta expression in chronic liver diseases and liver carcinoma

BACKGROUND. Estrogen receptor- (ER ) is variably expressed in hepatocellular carcinoma (HCC) and is believed to be correlated with prognosis and survival. Recently, another estrogen receptor (ER ) has been identi\ufb01ed, but its relevance in liver diseases is unknown. METHODS. The expression of ER in the liver of 42 patients with HCC (10 with paired extratumoral tissues) and 26 with chronic liver disease without HCC was studied by a reverse transcriptase-polymerase chain reaction method, and correlated with the expression of ER and severity of the liver disease. RESULTS. Both ER and wild-type ER were found to be expressed more often in patients with chronic liver disease compared with those with HCC (69% vs. 45% [P 0.046] and 46% vs. 10% [P 0.0008], respectively). ERs were similarly expressed in HCC and in the paired extratumoral tissue. Wild-type receptors, either alone or together with the deleted mutants ER 5, were more often coexpressed in chronic liver disease (58%) than in HCC (29%); in 13 tumors (31%), either ER 5 or no receptors at all were detected (P 0.006). Hepatitis B virus (HBV)-related tumors either did not appear to express ERs or expressed ER 5 more often than hepatitis C virus (HCV)-related tumors (67% vs. 15%; P 0.007). The same was true for multinodular compared with single nodular tumors (50% vs. 19%; P 0.04). CONCLUSIONS. Both receptors were expressed in chronic liver disease and neoplastic livers demonstrating different patterns in relation to the etiology and clinical presentation of the tumor. These differences might underscore different pathogenetic mechanisms in HBV-related and HCV-related HCC and a different evolutionary course for the tumo