VARIANT LIVER ESTROGEN-RECEPTOR TRANSCRIPTS ALREADY OCCUR AT AN EARLY-STAGE OF CHRONIC LIVER-DISEASE

Variant estrogen receptors may be found in hepatocellular carcinoma an d may influence its natural history Because it is not known whether th eir occurrence is an early or a late event during the course of chroni c liver disease or whether they cluster in some subgroups of patients, we investigated a series of patients in different stages of chronic l iver disease, One hundred eleven consecutive patients were studied for variant estrogen receptor transcripts by reverse-transcription polyme rase chain reaction of RNA extracted from liver biopsy specimens. In c hronic active hepatitis, variant estrogen receptor transcripts were co expressed with wild-type significantly more often in men than in women (P = .029) and in hepatitis B surface antigen (HBsAg)-positive subjec ts than in subjects positive for antibody to hepatitis C virus (P = .0 006). In hepatocellular carcinoma, again in men (P = .004) and in HBsA g-positive patients (P = .0015), the variant estrogen receptor transcr ipt was overexpressed or remained the only one expressed, Patients wit h liver cell dysplasia presented with the same estrogen receptor patte rn than patients with hepatocellular carcinoma, This further reinforce s the significance of liver cell dysplasia as a preneoplastic conditio n. The significantly higher occurrence of variant estrogen receptor in men (especially in HBsAg-positive men) already at an early stage of d isease, like chronic active hepatitis, suggests that the alteration of estrogen receptors, favoring uncontrolled proliferation and developme nt of hyperplasia, might constitute a prominent mechanism facilitating neoplastic transformation especially in men.