Hepatocellular carcinoma (HCC) is the most common primary tumor of liver and its incidence continues to increase worldwide. HCC is a disease with multifactorial causes and genetic variability has been discussed as a risk factor for its development. Liver is a hormone-sensitive organ and therefore is influenced by gonadal hormones, such as estrogen. Estrogen is known to participate in various biological functions, but its role in development of HCC, on the other hand, is controversial and presents evidence suggesting a role as both a carcinogen and protective effect in liver. Estrogen way of action is mediated by estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ), that belong to a family of nuclear receptors that may regulate the expression of many genes. The ER subtypes exert a variety of roles in many stages of liver disease and may play a part in the process of signal transduction, according to some studies. However, the many functions of ER subtypes in hepatic diseases, in special of the ERβ, are yet to be clarified. The genetic modifications related to HCC are not yet fully clarified and accumulation of multiple genetic alterations appears to have an important role in carcinogenesis of HCC. The presence of some certain single nucleotide polymorphism (SNP) may have a functional repercussion related to final product of a gene, which can be measured and may participate in some alterations related to a pathological condition. Our hypothesis is based on the fact that liver tissue express ER and its different variants exert multiple functions in various stages of liver disease and participate in an extremely complicated signal transduction process, therefore we believe that the presence of one or more SNPs of ESR1 and ESR2 genes may be related with the increase of risk in developing and the severity of HCC, as well as in the response to different treatments. The confirmation of our hypothesis by scientific studies may provide knowledge of markers that act as prognostic factors of this disease, as well as enabling alternatives to development of anti tumoral therapies.

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Background and aim: hepatocellular carcinoma is a type of cancer related with inflammation, as 90% of cases develop in a chronic inflammation condition. Excess inflammation can affect tissue homeostasis. Cytokines and inflammatory mediators are immunological components that can influence the functioning of cells and tissues. In addition, the estrogen receptor appears to play an important role in hepatocarcinogenesis. The aim of the study was to evaluate the expression of inflammatory markers and ER in patients with hepatocellular carcinoma. Methods: data from 143 patients of ISCMPA were analyzed. Immunohistochemistry was performed of cyclooxygenase-2 enzyme (COX-2), nuclear factor kappa B (NF-κB), tumor necrosis factor alpha (TNF-α) and ER in paraffin-embedded hepatic tissue. The percentage of the stained area, intensity of staining and of the number of ER positive nuclei were evaluated using the ImageJ 1.50 software.Results and conclusion: there was a significant difference between the groups in terms of the percentage of marked area (p = 0.040) for COX-2 and the intensity of staining of TNF-α (p = 0.030). No significant differences were observed in any of other parameters evaluated. In conclusion, COX-2 and TNF-α are possible markers that should be further studied to determine their immunohistochemical profile and role in HCC development.