الفهرس 
INRODUCTIONOnly 14 pages are availabe for public view
 |  | from | 111 |  |  |
| | | from | 111 | | |
Abstract
HCC is considered to be the commonest type of primary liver cancer. It is ranked as the sixth commonest type of cancer and the third cause of cancer related deaths. HCC has several risk factors. It has no specific symptoms or signs which is the main problem of HCC; the late diagnosis and poor prognosis.
Screening program is adopted in many countries in a trial for the early detection of HCC where curative treatment modalities are effective and thus improve the 5- year survival rate of patients. The available reliable tool of screening is abdominal U/S which is recommended to be done every six months. AFP is no longer supported as a screening tool.
Diagnosis of HCC depends mainly on radiological tools mainly triphasic CT abdomen. AFP is no longer the cornerstone in HCC diagnosis as it used to be. Recent studies reported its elevation in non-malignant conditions as well as non- hepatic malignancies.
It is obvious now the urgent need to develop a non- invasive diagnostic biomarker for the early detection of HCC. Recent studies revealed that hepatocarcinogenesis is a complex process where aberrant genetic and epigenetic changes are responsible for its development. They revealed also the importance of studying CTCs in the peripheral blood of patients with HCC.
The commonest epigenetic change reported is aberrant DNA methylation. It is reported to be an early event in hepatocarcinogenesis that results in silencing of TSGs as RASSF1A. Assessment of the methylation status of TSGs can be used as a diagnostic tool for the early diagnosis of HCC. RASSF1A is a TSG which is commonly methylated in HCC which leads to its transcriptional silencing and thus lose its function as TSG.
MSP was used in the present study to assess the methylation status of RASSF1A promoter. This study was conducted on three groups: 20 patients with newly diagnosed HCC on top of HCV- related cirrhosis, 20 patients with HCV-related cirrhosis and 20 persons as a control group with matched age and sex. Samples were collected from the patients before receiving any form of treatment for either HCC or HCV.
MSP depended mainly on three steps: first extraction of DNA from the sera of the patients and the controls, second the bisulphite conversion of the extracted DNA that cause the conversion of unmethylated cytosine into uracil, but it has no effect on methylated cytosine that remain unchanged. Further PCR was used for in the detection of methylation status of the promoter of RASSF1A.
As regards the aberrant methylation of RASSF1A; in this study it was detected in 13(65%) patients out of 20 patients with HCC. Furthermore; in our study the methylation of RASSF1A was completely absent in the control group (100%) who had unmethylated RASSF1A. In cirrhotic group RASSF1A aberrant hypermethylation was detected in only 6 patients (30%) out of 20 cirrhotic patients.