Villa Erica, Grottola Antonella, Colantoni Alessandra, De Maria Nicola, Buttafoco Paola, Ferretti Ilva, Manenti Federico
Department of Internal Medicine, Division of Gastroenterology, University of Modena and Reggio Emilia, 41100 Modena, Italy.
Ann N Y Acad Sci. 2002 Jun;963:37-45.
Experimental and clinical evidence indicates that estrogens have a relevant role in the pathogenesis of cancer of hormone-sensitive organs. Estrogen receptors (ERs) are present in liver cells. Normal liver expresses almost exclusively wild-type ERs derived from the full-length transcript of the gene. During progression of liver disease to hepatocellular carcinoma, variant forms of ERs have been demonstrated that greatly influence the course of the disease and the possibility of palliative treatment. Peritumoral cirrhotic tissue of patients with hepatocellular carcinoma, especially males, expresses a variant form of ER (vER) with an exon 5 deletion. In hepatocellular carcinoma, vER largely predominates and sometimes becomes the only form expressed. That the occurrence of vER alone is limited almost exclusively to males suggests that it could be one of the molecular events that eventually lead to the preferential development of hepatocellular carcinoma in males. In addition, the presence of vER appears most frequently in patients infected with the hepatitis B virus. The growth rate of hepatocellular carcinoma in patients with vER is also significantly higher than that in patients with tumors expressing wtER.
实验和临床证据表明，雌激素在激素敏感器官癌症的发病机制中具有重要作用。雌激素受体（ERs）存在于肝细胞中。正常肝脏几乎只表达源自该基因全长转录本的野生型ERs。在肝病发展为肝细胞癌的过程中，已证实ERs的变体形式会极大地影响疾病进程和姑息治疗的可能性。肝细胞癌患者，尤其是男性患者的瘤周肝硬化组织表达一种外显子5缺失的ER变体形式（vER）。在肝细胞癌中，vER占主导地位，有时甚至成为唯一表达的形式。vER的出现几乎仅局限于男性，这表明它可能是最终导致男性肝细胞癌优先发生的分子事件之一。此外，vER最常出现在感染乙肝病毒的患者中。vER患者的肝细胞癌生长速度也明显高于表达wtER肿瘤的患者。
