Estrogen Receptor Classification for Hepatocellular Carcinoma: Comparison With Clinical Staging Systems

Villa, Erica; Colantoni, Alessandra; Cammà, Calogero; Grottola, Antonella; Buttafoco, Paola; Gelmini, Roberta; Ferretti, Ilva; Manenti, F.

doi:10.1200/jco.2003.11.051

Cited by 59 publications

(54 citation statements)

References 16 publications

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“…These tumors were responsive to megestrol and unresponsive to anti estrogen tamoxifen. High rates of vERα expression have been shown to be present in men at high risk of HCC development [56,57] . In patients with chronic hepatitis and cirrhosis, the expression of vERα has been associated with higher oxidative stressinduced DNA damage and c-myc mRNA expression, a factor indicating increased genomic instability, augmented cytoproliferation and carcinogenesis [5] .…”

Section: Estrogen Receptormentioning

confidence: 99%

Role of sex steroid receptors in pathobiology of hepatocellular carcinoma

Kalra¹,

Mayes²,

Assefa³

et al. 2008

WJG

133

116

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The striking gender disparity observed in the incidence of hepatocellular carcinoma (HCC) suggests an important role of sex hormones in HCC pathogenesis. Though the studies began as early as in 1980s, the precise role of sex hormones and the significance of their receptors in HCC still remain poorly understood and perhaps contribute to current controversies about the potential use of hormonal therapy in HCC. A comprehensive review of the existing literature revealed several shortcomings associated with the studies on estrogen receptor (ER) and androgen receptor (AR) in normal liver and HCC. These shortcomings include the use of less sensitive receptor ligand binding assays and immunohistochemistry studies for ERα alone until 1996 when ERβ isoform was identified. The animal models of HCC utilized for studies were primarily based on chemical-induced hepatocarcinogenesis with less similarity to virus-induced HCC pathogenesis. However, recent in vitro studies in hepatoma cells provide newer insights for hormonal regulation of key cellular processes including interaction of ER and AR with viral proteins. In light of the above facts, there is an urgent need for a detailed investigation of sex hormones and their receptors in normal liver and HCC. In this review, we systematically present the information currently available on androgens, estrogens and their receptors in normal liver and HCC obtained from in vitro , in vivo experimental models and clinical studies. This information will direct future basic and clinical research to bridge the gap in knowledge to explore the therapeutic potential of hormonal therapy in HCC.

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Section: Estrogen Receptormentioning

confidence: 99%

Role of sex steroid receptors in pathobiology of hepatocellular carcinoma

Kalra¹,

Mayes²,

Assefa³

et al. 2008

WJG

133

116

View full text Add to dashboard Cite

show abstract

“…It is worth noting that a variant form of the wild-type estrogen receptor (wtER) that maintains a constitutive transcriptional activity has been described [22]. Compared with HCCs expressing wtER, HCCs with variant ER (vER) had more aggressive clinical features and insensitivity to tamoxifen [23,24]. In a preliminary, prospective, randomized study of 45 patients with HCC characterized by vER, patients treated with megestrol had a significantly longer median survival time than untreated patients (19 months vs. 7 months; p = .0090) [25].…”

Section: Hormonal Therapymentioning

confidence: 99%

Systemic Therapy of Advanced Hepatocellular Carcinoma: How Hopeful Should We Be?

2006

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Worldwide, hepatocellular carcinoma (HCC) is the fifth most common cancer and the third most common cause of cancer-related death. In the U.S., 18,510 new cancers of the liver and intrahepatic bile duct are expected in 2006, with an estimated 16,200 deaths. The incidence rates for HCC in the U.S. continued to rise steadily through 1998 and doubled during the period 1975-1995. Unresectable or metastatic HCC carries a poor prognosis, and systemic therapy with cytotoxic agents provides marginal benefit. A majority of HCC patients (>80%) presents with advanced or unresectable disease. Even for those with resected disease, the recurrence rate can be as high as 50% at 2 years. Because of the poor track record of systemic therapy in HCC, there has been a sense of nihilism for this disease in the oncology community for decades. However, with the arrival of newly developed molecularly targeted agents and the success of some of these agents in other traditionally challenging cancers, like renal cell carcinoma, there has recently been renewed interest in developing systemic therapy for HCC. This review attempts to concisely summarize the historical perspective and the current status of systemic therapy development in HCC. The Oncologist

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“…As previously reported, ERs, which consist of ERa and ERb, exist not only in female endocrine cells, but also in many types of epithelial cells, including hepatocytes in healthy, cirrhotic, or carcinomatous liver tissue. [14][15][16][17][18][19] ERs in hepatocytes mediate estrogen-responsive biological effects through either DNA binding or in a DNA-independent manner. 20 Regarding nongenomic estrogen signaling, Naugler et al reported, in a murine model, that ERa interferes with interleukin-6 (IL-6)-associated HCC genesis.…”

mentioning

confidence: 99%