We report the case of a 19-year-old woman who presented with a hepatic mass without cirrhosis. Light microscopy revealed a cholangiocarcinoma having both well-differentiated adenocarcinoma and lymphoepithelioma-like undifferentiated carcinoma components. By immunohistochemistry, the tumor showed strong and diffuse expression for cytokeratin AE1, 5D3, and CK22. The tumor cells were positive for p53 protein (more than 75% of the cells) but negative for bcl-2 and LMP1. Abundant Epstein-Barr virus EBER (1/2) oligonucleotides were detected in both tumor components, but not in the lymphoid stroma or the nontumor liver. To the best of our knowledge, this is the third report of an Epstein-Barr virus-associated primary hepatobiliary adenocarcinoma with lymphoepithelioma-like component. Int J Surg Pathol 8(4):347-351, 2000
The incidence of p53 gene abnormalities in human hepatocellular carcinoma (HCC) varies in different geographical areas, being higher in regions where hepatitis virus infection and dietary exposure to aflatoxin B1 are the most common aetiological agents. These mutations are less frequently encountered in Europe, although some studies have reported p53 protein overexpression in up to 45% of cases analysed. We have analysed 129 tumour samples of primary malignant hepatic neoplasms recovered from paraffin blocks processed in two pathology laboratories in a Mediterranean area of Spain (Valencia and Gerona). Among 14 cases in which p53 immunohistochemistry expression proved positive, 5 stained in more than 50% of the cell nuclei. By PCR-SSCP analysis we could detect the complete sequence from exon 5 through 8 in 70 cases and part of this region in the remaining cases, but no mutations were found. We found no relationship with the clinical stage, tumour stage or clinical outcome. We conclude that p53 gene alterations are not a major event in the malignant transformation of hepatic cells in this region of the Mediterranean. The variable incidence of p53 gene alterations in other geographical areas may reflect a different genetic background for the aetiology of HCC.
The prevalence of human liver cancer shows a broad spectrum of variation in distinct geographical regions, depending on different risk factors, and their pathogenesis is poorly understood. We study the significance of molecular alterations of K-ras gene in human liver carcinomas in a low-incidence region such as a Mediterranean area of Spain (Valencia and Gerona). Our results reveal a low incidence of K-ras codon 12 mutations in hepatocellular carcinomas (HCC) and a higher incidence in cholangiocarcinomas (CCC). Similar results have been obtained in high-risk areas. We conclude that K-ras gene mutations are not a major event in the malignant transformation of hepatic cells in this region of the Mediterranean but that molecular implications of hepatocellular and cholangiocarcinomas appear to be different. Int J Surg Pathol 8(4):267-270, 2000
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