1[]Hoda A El-Aggan, 2Sherif E Hegab, 3Nahed M Baddour, 4Amal F Ketat.
Departments of 1Medicine
(Hepatobiliary Unit), 2Radiology, 3Pathology and
4Medical Biochemistry, Faculty of Medicine, University of
Alexandria, Egypt.
Angiogenesis is an essential process for growth and metastasis of various cancer cells. Since hepatocellular carcinoma (HCC) is a typical hypervascular tumor, the purpose of this study was to evaluate the relationship between angiogenin (ANG) (which is best known for its in vivo angiogenic activity) and tumor vascularity, differentiation and proliferative activity in HCC. To clarify this relationship, serum ANG levels were measured in 30 patients with histologically-confirmed HCC of variable sizes, 30 patients with cirrhosis and in 20 healthy subjects using enzyme-linked immunosorbant assay. Tumor vascularity of HCC was assessed by color Doppler sonography in terms of the pulsatile flow pattern, the resistive index, the pulsatility index and the hepatic tumor index. Also, tumor vascularity was histologically quantitated as the intratumor microvessel area (MVA) using a computerized image analysis system in core liver biopsy specimens obtained from 18 HCC patients. Moreover, tumor differentiation classified according to Edmondson's grading system and tumor proliferative activity assessed by proliferating cell nuclear antigen-labeling index (PCNA-LI), were studied in all liver biopsies. In patients with HCC, the serum ANG levels were significantly higher than those in patients with cirrhosis and healthy subjects and showed a positive correlation with the intratumor MVA (P < 0.05). Moreover, the serum ANG levels and the intratumor MVA were well correlated with Edmondson's grade, PCNA-LI and tumor size in HCC patients (P < 0.05). Among color Doppler measurements, the hepatic tumor index (but not the resistive index or the pulsatility index of tumor vessels) showed direct correlations with serum ANG levels, intratumor MVA, Edmondson's grade and PCNA-LI (P < 0.05). Meanwhile, these parameters showed significant increases in patients with peritumoral and intratumoral pulsatile flow compared with those in patients with peritumoral pulsatile flow only (P < 0.05). On the other hand, there were no significant relationships between serum ANG levels and age, hepatitis virus status, serum albumin, serum bilirubin, Child-Pugh score and serum a- fetoprotein in HCC patients (P > 0.05). In conclusion, excessive ANG production in HCC may contribute to tumor angiogenesis, differentiation and proliferative activity suggesting a potential role for the use of ANG antagonists in the treatment of HCC. Serum ANG may be a useful tumor marker for the assessment of HCC.
[] Correspondence: Hoda A. El-Aggan,
Hepatobiliary Unit, Department of Medicine, Faculty of Medicine, Alexandria
University.