The clinical and pathogenetic significance of estrogen receptor-beta expression in chronic liver diseases and liver carcinoma.
BACKGROUND
Estrogen receptor-alpha (ERalpha) is variably expressed in hepatocellular carcinoma (HCC) and is believed to be correlated with prognosis and survival. Recently, another estrogen receptor (ERbeta) has been identified, but its relevance in liver diseases is unknown.


METHODS
The expression of ERbeta 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 ERalpha and severity of the liver disease.


RESULTS
Both ERbeta and wild-type ERalpha 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 ERdelta5, were more often coexpressed in chronic liver disease (58%) than in HCC (29%); in 13 tumors (31%), either ERdelta5 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 ERdelta5 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.
Iavarone
Massimo
M
A.M. and A. Migliavacca Center, Division of Hepatology and FIRC Liver Cancer Unit, IRCCS Maggiore Policlinico Hospital, University of Milan, Milan, Italy. massimo.colombo@unimi.it
Lampertico
Pietro
P
Seletti
Chiara
C
Francesca Donato
Maria
M
Ronchi
Guido
G
del Ninno
Ersilio
E
Colombo
Massimo
M
D000368:Aged; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000378:metabolism* / Q000473:pathology* / Q000821:virology; D002908:Chronic Disease; D017931:DNA Primers / Q000737:chemistry; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D005260:Female; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification; D006509:Hepatitis B / Q000821:virology; D006514:Hepatitis B Surface Antigens / Q000378:metabolism; D006515:Hepatitis B virus / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D008107:Liver Diseases / Q000209:etiology / Q000378:metabolism* / Q000473:pathology* / Q000821:virology; D008113:Liver Neoplasms / Q000209:etiology / Q000378:metabolism* / Q000473:pathology* / Q000821:virology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017384:Sequence Deletion; D012689:Sequence Homology, Nucleic Acid
D017931:DNA Primers; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D006514:Hepatitis B Surface Antigens; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011960:Receptors, Estrogen