الفهرس 
INTRODUCTION & AIM OF THE WORKOnly 14 pages are availabe for public view
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Abstract
Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and the third most common cause of cancer death. In Egypt, the burden of HCC has been markedly increased in the last few years mainly due to the high incidence of HCV infection which is the major risk factor of liver cirrhosis induced HCC. HCC is a complex disease with wide spectrum of morphological and molecular patterns. Angiogenesis plays an important role in HCC growth and metastasis.
Vascular endothelial growth factors (VEGF) are a group of angiogenesis-promoting proteins that play a crucial role in primary tumor growth, invasion and metastasis. VEGF-A is the most important and well characterized member. Splicing of VEGFA gene produce several isoforms , angoigenic isoforms including VEGF121, VEGF145, VEGF165, VEGF189 and VEGF206 and antiangiogenic isoforms including VEGF121b, VEGF145b, VEGF165b, VEGF189b and VEGF206b .
Targeting angiogenesis is one of the lines of HCC treatment. The only approved antiangiogenic drug targeting HCC is sorafenib, through inhibition of VEGF receptor(VEGFR)and platelet-derived growth factor receptor (PDGFR). Numerous other agents target circulating VEGF (eg, bevacizumab and cabozantinib ) and selective isoform 165 target therapy (Pegaptanib ).
Despite the improved overall survival with sorafenib in advanced HCC, clinical studies till now suggest only a modest survival benefit with anti-VEGF therapy and drug resistance in some cases. Patient molecular preselection for individualization of therapy is recommended for better management of HCC.
Therefore, this study aimed to study immunohistochemical expression of VEGF in both HCC with adjacent non tumorous tissue and nonmalignant liver lesions to evaluate the stepwise pathogenic role of VEGF in carcinogenic process and correlate it with the clinicopathological parameters of HCC. Also, this study aimed to study different VEGF isoforms expressed in HCC and adjacent non tumorous tissue by reverse transcriptase PCR for better therapy selection.
This was a retrospective study included 96 liver specimens from patients presented with hepatocellular lesions and the studied cases were divided into HCC (49 cases) and non-malignant group (cirrhosis (12 cases), chronic viral hepatitis (21 cases) and normal liver (14 cases).
The median age of HCC cases was 58 years with predominance of male gender 77.6%. Median level of serum AFP was 18.5ng/ml and also 98% of cases were positive for hepatitis viral infection. Solitary lesions were presented in 71.4% of cases with median tumor size was 4.5 cm. All our cases 100% were of classic HCC type and showed moderately differentiated grade in 65.3% of cases and poorly differentiated in 34.7% of cases. StageT1 were present in 34.7%, stage T2 in 59.2% and stage T3a in 6.1 % of cases. Microscopic vascular invasion present in 53.1% of cases. Adjacent liver tissue showed cirrhotic changes in 77.6% of cases and 22.4% of cases showed features of chronic viral hepatitis (non -cirrhotic).
The current study showed there was a statistical significant higher level of mean of VEGF H-score expression in adjacent non tumorous tissue than HCC (P>0.001) with 75.5% of cases showed VEGF expression in HCC less than or equal adjacent non tumorous tissue (T≤N) and 24.5% of cases showed VEGF expression in HCC more than adjacent non tumorous tissue (T < N). Highly statistical significant difference was observed by comparing the mean values of VEGF H score between the studied cases of cirrhosis, chronic hepatitis, normal liver groups, adjacent non tumorous tissue and HCC group (P<0.001) with cirrhotic group showed the highest level of VEGF expression. VEGF showed significant correlation as regard adjacent non tumorous tissue (higher in non- cirrhotic adjacent non tumorous tissue than in cirrhotic adjacent non tumorous tissue)
There is no significant correlation between VEGF expression and different clinicopathological parameters including mean vascular density assessed by CD34 immunostaining.