الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
HCC is a lethal disease that carries a poor prognosis and impairs quality of life of such patients it isthe fifth commonest malignancy accounting for 6% of all malignant lesions. This raised the need for efficient feasible Screening, diagnostic and treatment modalities.
Identification of early HCC which is potentially amenable to aggressive intervention and improved survival is the rationale behind screening for HCC. An effective screening program, however, requires certain criteria to be successful, including the following: a common disease with substantial mortality, an identifiable target group, acceptable tests with high sensitivity and specificity, and available treatment.
AFP has been utilized as a marker for HCC, despite its low sensitivity and positive predictive value. Moreover, it has been estimated that up to 40% of HCC patients have normal AFP levels.(212) Therefore, novel biomarkers are needed to be used for early detection of cases with HCC.
Angiogenesis, is critical for the growth and progression of various human solid tumors because it enables delivery of oxygen and nutrients.(213)Significant HCC growth is dependant on angiogenesis, and an increase in tumor dimension beyond 0.5 mm will induce the proliferation of vascular endothelial cells.(214)Among the known angiogenic factors, VEGF has emerged as the central regulator of the angiogenic process in physiological and pathological conditions. VEGF mediates its angiogenic effects via several different receptors. VEGF receptor (VEGFR) 1 and VEGFR2 were originally discovered on endothelial cells as tyrosine kinase receptors. The various members of the VEGF family have different binding affinities for each receptor.VEGFR1 plays an important role in developmental angiogenesis as well as other processes.
The VEGF family comprises 6 glycoproteins; VEGFA,VEGF-B, VEGF-C, VEGF-D, VEGF-E, and placental growth factor. Within these major VEGF subtypes are multiple isoforms. The best-characterized VEGF family member is VEGF-A (commonly referred to as VEGF). The human VEGF-A transcript undergoes alternative splicing to yield mature proteins of 121, 145, 165, 183, 189, and 206 amino acids; VEGF-165 is the predominant isoform.(215)
NRP-1 is a protein that in humans is encodedby the NRP1 gene. This is one of two human neuropilins. NRP-1 was first identified as a 120–130 kDa membrane protein from the optic tract of XenopuslaevisIt,(216)andfunctions as a semaphorin (SEMA) receptor in the developing nervous system.(217-219)Subsequently, NRP-1 was found to be a co-receptor for vascular endothelial growth factor 165 (VEGF 165) and is expressed in endothelial cells (EC), where it is involved in the regulation of angiogenesis and endothelial cell migration.(131,220,221)Overexpression of NRP-1 in a transgenic mouse model increased capillary and blood vessel formation and resulted in hemorrhage,(122)whereas functional inactivation of NRP-1 in mice led to embryonic lethality with multiple vascular abnormalities, including of avascular regions, heterogeneous blood vessel size and abnormally formed dorsal aorta.(124)Theresults indicated that NRP-1 was a key regulator of developmental angiogenesis.
The aim of our study was to evaluate the tissue expression of neuropillin-1 and VEGF in HCC.
This study was carried on 27 HCC patients diagnosed by AFP and abdominal triphasic CT recruited from the Hepatobiliary unit of the Main Alexandria University Hospital. and they were subjected to per-cutanous U.S guided fine needle aspiration cytology using immune-histo-chemistry technique for detection of both NRP-1 and VEGF expression in both tumorous and peri-tumorous tissue.