The clinical and pathogenetic significance of estrogen receptor‐β expression in chronic liver diseases and liver carcinoma

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Abstract
BACKGROUND Estrogen receptor‐α (ERα) is variably expressed in hepatocellular carcinoma (HCC) and is believed to be correlated with prognosis and survival. Recently, another estrogen receptor (ERβ) has been identified, but its relevance in liver diseases is unknown. METHODS The expression of ERβ 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 ERα and severity of the liver disease. RESULTS Both ERβ and wild‐type ERα 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 ERδ5, were more often coexpressed in chronic liver disease (58%) than in HCC (29%); in 13 tumors (31%), either ERδ5 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 ERδ5 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 tumor. Cancer 2003;98:529–34. © 2003 American Cancer Society. DOI 10.1002/cncr.11528