Detection of Hepatocellular Carcinoma
Background: Tumor markers in the early detection of tumors are promising tools that could improve the control and treatment of tumors. While alpha-fetoprotein (AFP) is a commonly used tumor marker in the detection of hepatocellular carcinoma (HCC), its sensitivity and specificity are insufficient to detect HCC in all patient samples.
Methods: We compared AFP with serum levels of vascular endothelial growth factors (VEGF and VEGF-A), insulin- like growth factor-2 (IGF-II), and the activity of the lysosomal enzyme alpha-L-fucosidase (AFU) in the sensitivity of detection of HCC and cirrhosis in Egyptian patients.
Results: The sensitivity of tumor detection using AFP was 68.2%. This level of detection was increased to 88.6% when AFP was evaluated in conjunction with AFU. The combined use of AFP and VEGF increased the sensitivity of detection to 95.5% in patients with HCC. The combination of the three markers yielded 100% detection sensitivity. VEGF-A showed a low specificity (20%), and IGF-II showed extremely low sensitivity (4.5%).
Conclusions: We suggest that AFU or VEGF or both be measured with AFP to improve the detection sensitivity of HCC.

Hepatocellular carcinoma (HCC) is a common malignancy worldwide and is the main cause of mortality in patients with chronic liver diseases. For example, liver cirrhosis is a precancer condition that in many cases can develop into HCC. Therefore, cirrhotic patients are usually screened for HCC during their follow-up procedure.

Tumor markers are potential screening tools that are widely used for early diagnosis of tumors. Many research groups are evaluating the sensitivity of available tumor markers and also are investigating the development of novel markers. The primary marker for HCC is a-fetoprotein (AFP), a single polypeptide chain glycoprotein. Generally, AFP shows acceptable sensitivity; however, AFP is not secreted in all cases of HCC and may be normal in as many as 40% of patients with early HCC.

We studied methods to improve the detection of HCC by measuring AFP in addition to other suggested biochemical factors for the same sample. Among these factors is a-L-fucosidase (AFU), a lysosomal enzyme present in all mammalian cells. AFU has been proposed as a tumor marker since many studies reported increased AFU serum levels in patients with cirrhosis and HCC. At the same time, it is not correlated to AFP level in serum.

We also investigated vascular endothelial growth factor (VEGF), the angiogenic glycoprotein, which was previously reported to express high serum levels in patients with HCC. Since HCC is characterized by hypervascularity, it is likely to produce angiogenic factors such as VEGF, causing proliferation of the hepatic sinusoidal endothelial cells. We also studied VEGF-A, a subtype of VEGF. High VEGF-A levels have been reported in patients with hepatic ascites.

We also examined the levels of the polypeptide hormone insulin-like growth factor II (IGF-II) in patients with cirrhosis and HCC. The level of IGF-II in serum showed a degree of sensitivity toward HCC. IGF-II levels have been reported as markedly lower than normal in patients with primary HCC. Other studies reported an increase of IGFII levels in early HCC in experimental animal models. IGF-II is mainly produced by liver cells and is probably affected by liver disorders.

In all of these markers, we determined serum levels for 13 normal individuals, for 20 patients with cirrhosis, and for 44 patients with HCC. An extensive statistical analysis of given data was used to calculate the sensitivity, specificity, and diagnostic accuracy for each marker. A combined evaluation was also carried out for AFP with AFU and VEGF. The receiver operating characteristic (ROC) curve was used for further evaluation and comparison of data.