Villa E, Dugani A, Moles A, Camellini L, Grottola A, Buttafoco P, Merighi A, Ferretti I, Esposito P, Miglioli L, Bagni A, Troisi R, De Hemptinne B, Praet M, Callea F, Manenti F
Department of Internal Medicine, University of Modena, Italy.
Hepatology. 1998 Apr;27(4):983-8. doi: 10.1002/hep.510270413.
Variant estrogen receptors may be found in hepatocellular carcinoma and may influence its natural history. Because it is not known whether their occurrence is an early or a late event during the course of chronic liver disease or whether they cluster in some subgroups of patients, we investigated a series of patients in different stages of chronic liver disease. One hundred eleven consecutive patients were studied for variant estrogen receptor transcripts by reverse-transcription polymerase chain reaction of RNA extracted from liver biopsy specimens. In chronic active hepatitis, variant estrogen receptor transcripts were coexpressed with wild-type significantly more often in men than in women (P = .029) and in hepatitis B surface antigen (HBsAg)-positive subjects than in subjects positive for antibody to hepatitis C virus (P = .0006). In hepatocellular carcinoma, again in men (P = .004) and in HBsAg-positive patients (P = .0015), the variant estrogen receptor transcript was overexpressed or remained the only one expressed. Patients with liver cell dysplasia presented with the same estrogen receptor pattern than patients with hepatocellular carcinoma. This further reinforces the significance of liver cell dysplasia as a preneoplastic condition. The significantly higher occurrence of variant estrogen receptor in men (especially in HBsAg-positive men) already at an early stage of disease, like chronic active hepatitis, suggests that the alteration of estrogen receptors, favoring uncontrolled proliferation and development of hyperplasia, might constitute a prominent mechanism facilitating neoplastic transformation especially in men.
在肝细胞癌中可能发现变异型雌激素受体，其可能影响肝细胞癌的自然病程。由于尚不清楚它们的出现是慢性肝病病程中的早期还是晚期事件，也不清楚它们是否在某些患者亚组中聚集，我们对一系列处于不同阶段的慢性肝病患者进行了研究。通过对肝活检标本提取的RNA进行逆转录聚合酶链反应，对111例连续患者的变异型雌激素受体转录本进行了研究。在慢性活动性肝炎中，变异型雌激素受体转录本与野生型共表达的情况在男性中显著多于女性（P = 0.029），在乙肝表面抗原（HBsAg）阳性患者中显著多于丙型肝炎病毒抗体阳性患者（P = 0.0006）。在肝细胞癌中，同样在男性（P = 0.004）和HBsAg阳性患者中（P = 0.0015），变异型雌激素受体转录本过度表达或成为唯一表达的转录本。肝细胞发育异常患者的雌激素受体模式与肝细胞癌患者相同。这进一步强化了肝细胞发育异常作为肿瘤前状态的重要性。在疾病早期，如慢性活动性肝炎时，男性（尤其是HBsAg阳性男性）变异型雌激素受体的发生率显著更高，这表明雌激素受体的改变有利于不受控制的增殖和增生发展，可能是促进肿瘤转化的一个重要机制，尤其是在男性中。
