The Expression of Estrogen Receptors in Hepatocellular Carcinoma in Korean Patients

Abstract

Expression of estrogen receptors (ER)-α and -β, 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-α 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-α variant was independent of sex (100% female vs. 91.3% male) and HCV and HBV status (91.3% vs. 100%). Wild-type ER-β was expressed more often in HCV patients than in HBV patients (95.7% vs. 44.4%; p < 0.05). In conclusion, the stronger ER-α 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-α variant (vER-α) is not related to male HCC prevalence. In addition, the predominant expression of ER-β in HCV patients suggests that it plays an important role in HCV-induced liver disease.

Role of sex steroid receptors in pathobiology of hepatocellular carcinoma

“…Tavian et al [71] found higher AR mRNA levels in tumor than in the corresponding peri-tumoral tissue in a relatively small percentage of HCC samples, suggesting that AR mRNA levels are associated with the histological tumor differentiation showing a lower AR expression in poorlydifferentiated HCC than in well-differentiated tumors. In contrast, AR levels in Korean population with HCC do not show differences between tumor and peri-tumor tissues using RT-PCR [52] . Due to these conflicting reports on AR expression in HCC, there is a need for detailed investigation of AR mRNA as well as protein levels using more sensitive and accurate detecting quantitative methods.…”

“…Table 2 gives the details of these studies [18,19,40,45,51,52] . In situ hybridization using ER specific oligonucleotide sequence probe revealed that 11 out of 15 HCC tissue samples expressed ER mRNA [40] .…”

“…Breast cancer studies sug gest that ERα:ERβ expression ratio changes during carcinogenesis and is believed to play a role in tumor development [58] . Recently, Wang et al [52] studied the expression of ERα and ERβ in HCC tissues of Korean population using RT-PCR, and assessed 32 tumoral and peritumoral tissues from HCC patients with underlying chronic HBV or HCV …”

“…Since then, several reports showing protein and mRNA expression of AR in liver have been published. Table 3 [13,15,17,28,[30][31][32][33]35,40,41,52,[59][60][61][62][63][64] and Table 4 [ [14][15][16][17]31,[33][34][35][36]39,41,47,52,[65][66][67][68][69][70][71] give the details of these studies. In general, AR is found to be over expressed in liver tumor compared to the adjacent nor mal tissue [15,17,33,36,38] .…”

Androgen Receptor and Hepatocellular Carcinoma

“…There are several reports concerning the expression of AR mRNA and AR protein in tumor and in non-tumor parts of liver, suggesting that AR plays an important role in hepatocarcinogenesis [6,[16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35].…”