The expression of estrogen receptors in hepatocellular carcinoma in Korean patients

Abstract

Expression of estrogen receptors (ER)-alpha and -beta, as well as androgen receptor (AR), in hepatocellular carcinoma (HCC) is thought to be correlated with prognosis, survival, and male prevalence of HCC. These hypotheses are based on investigations of European patients; however the expression patterns of these receptors in Asian patients are largely unknown. In this study, we collected liver carcinoma and peritumor tissues from 32 patients (9 females and 23 males) in South Korea. The expression of ERs and ARs was studied using RT-PCR. Wild-type ER-alpha and AR were expressed in all of the samples investigated, and their expression was independent of the causal virus or patient sex. Expression of the ER-alpha variant was independent of sex (100% female vs. 91.3% male) and HCV and HBV status (91.3% vs. 100%). Wild-type ER-beta was expressed more often in HCV patients than in HBV patients (95.7% vs. 44.4%; p < 0.05). In conclusion, the stronger ER-alpha variant expression in HCC tissues implies that this variant has an important role in HCC development. However, at least in Korean patients, expression of the ER-alpha variant (vER-alpha) is not related to male HCC prevalence. In addition, the predominant expression of ER-beta in HCV patients suggests that it plays an important role in HCV-induced liver disease.

Fig. 1

The expression of AR and ER-α, -β in HCV and HBV patients as determined by RT-PCR analysis. (A) HCV patient. (B) HBV patient. ER-α (1), ER-α (2), ER-β (1), ER-β (2), and ER-β (3) are the ER-α, -β RT-PCR products using different primers (Table 1); S93 and 21 are patient identification numbers. The arrows show the vER-α bands. (C) AR expression in female and male HCV and HBV patients. N, peritumor tissues; T, tumor tissues.

Fig. 2

Immunohistochemical staining of AR in hepatocellular carcinoma and paired peritumor tissues. AR protein was present in the nuclei of all normal hepatic and hepatocellular carcinoma cells. No difference was found in the expression of AR between tumor and non-tumor tissues or according to the viral agent. (A) non-tumor region of an HCV patient: (B) tumor region of a HCV patient; (C) non-tumor region of a HBV patient; (D) tumor region of a HBV patient. Magnifications: 200 ×.