الفهرس 
AcknowledgmentOnly 14 pages are availabe for public view
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Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the third cause of cancer-related mortality worldwide.
This study aimed to evaluate the frequency of tumor suppressor genes (p16INK4a and RASSF1A) hypermethylation in tissue specimens from HCC patients and to detect their clinical significance.
In order to achieve this goal, twenty five patients confirmed to have HCC were selected and an equal number of patients with chronic liver disease due to hepatitis C virus (HCV) infection from Hepatology, Gastroenterology and Infectious diseases department, Benha University Hospital.
All patients included in the study were subjected to full history taking, thorough clinical examination, routine laboratory and radiological investigations. Additionally, Detection of promotor methylation status of RASSF1A and P16 using methylation specific PCR and detection of gene expression level of RASSF1A and P16 genes in liver tissue.
Our results revealed that HCC was presented more in males with a male to female ratio 2.5:1 and the mean age of patients with HCC was (58.4±7.71)years , ranging from (39-74). There was no statistically significant difference between the two patient groups regarding the residence, occupation or the special habits.
Abdominal pain was the commonest symptom in patients with HCC. Whereas hard liver was the commonest sign. The past history of schistosomiasis and Diabetes mellitus was present significantly in patients with HCC.
According to the laboratory investigations , the mean values of prothrombin time were significantly higher in HCC group than in the CLD group, but serum albumin was significantly lower in HCC group than in the CLD group. ). In the current study, alpha fetoprotein was significantly higher in HCC group compared to the CLD group.56% of the HCC group had alpha fetoprotein level (>400 ng/ml ).
Concerning Child classification, the majority of HCC patients were Child class A (68%) followed by Child class B (32 %) and none of patients were Child class C. As regard OKUDA staging of HCC patients, most of HCC patients were stage I (76 %) followed by stage II (24%), none of patients were stage III.
Abdominal ultrasonography showed a higher incidence of a single focal lesion (96%), right lobe focal lesions (84%) and hypoechoic lesions (80%).
In the current study, methylated RASSF1A gene in liver specimens was detected in 76% of HCC cases in comparison to 12% of CLD (chronic HCV) group and methylated P16 gene in liver specimens was detected in 68% of HCC cases in comparison to 28% of CLD group so the frequency of RASSF1A and P16 methylation were significantly higher in the HCC patients than CLD patients .
There was no statistically significant relationship between RASSF1A methylation pattern and age, Child classification , Okuda staging , alfa fetoprotein, characters of focal lesions and survival of HCC cases . The P16 methylation showed the similar results but the age was significantly higher in HCC patients who had methylated P16 gene (62.24±5.36) than those who had unmethylated P16 gene (50.25±5.15).
There was both RASSF1A and P16 gene under expression level in HCC group as compared to CLD. Also RASSF1A and P16 methylation lead to under expression in their related gene level .