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Is Alfa Feto Protein considered a Hepatocellular Carcinoma Marker or a Hepatocellular Marker ?

Ehab Hafiz

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and is a leading cause of cancer- related death worldwide. In the United States, HCC is the ninth leading cause of cancer deaths. Despite advances in prevention techniques, screening, and new technologies in both diagnosis and treatment, incidence and mortality continue to rise. Cirrhosis remains the most important risk factor for the development of HCC regardless of etiology.

AFP’s main function is the regulation of fatty acids in both fetal and proliferating adult liver cells.Since 1968, AFP has been used as a serum marker for the detection of HCC (Wong RJ, 2014).Several studies have evaluated the sensitivity and specificity of utilizing AFP with ranges of 21%–64% and 82%–93%, respectively (Colli A, 2000). One major disadvantage is that AFP levels can be falsely raised in patients who have active hepatitis but no evidence of HCC. The upper limit of normal that is often adopted is 20 ng/mL because AFP levels in healthy individuals rarely exceed this leve (Sherman M, 1995).Recently; AFP gene transcripts have been used as targets of the RT-PCR assay in blood from HCC patients but the detection of these gene transcripts do not truly reflect the presence of tumor cells, since non-tumors liver cells also abundantly express AFP mRNA, which could be released into blood because of hepatitis, liver cirrhosis and surgical injuries [Sakaida I. et al., 2004].

The melanoma antigen gene family (MAGE) consists of groups of genes: MAGE-A, B and C… These are all localized on the X chromosome at locations Xq28, Xq21.3, and Xq26, respectively. MAGE-A comprises 12 genes (MAGE-1–MAGE-12). The products of the MAGE family are highly specific to cancer cells; thus, they have been extensively studied as important tumor markers for cancer prognosis and immunotherapy. The members of MAGE gene family are highly expressed in human HCC. MAGE-1 and 3 are among these tumor associated antigens that play an extremely important role in tumor growth by rendering high, tumor cell metabolic rate. They encode 46 and 44 kDa proteins, respectively and are expressed in a very limited range of normal tissues (germ cells and placenta) [Christensen E, et al., 1984].

The study is conducted to examine the expression of MAGE-1, MAGE-3 and AFP gene transcripts in blood specimen obtained from patients with primary HCC and also from HCC-free controls to assess a multi-marker nested RT-PCR assay for the detection of circulating HCC cells and suggesting a diagnostic capability of these markers. Multimarker assay with cancer-specific MAGE-1 and MAGE-3 mRNAs and liver specific AFP mRNA appears to be a readily available and highly sensitive and specific method for the detection of circulating HCC cells. Since nested PCR utilizes a couple of internal primers to reamplify the specific PCR product, it exhibits higher sensitivity, stronger specificity and lower false-positive occurrence as compared to single RT.