الفهرس 
? Epidemiology of HCCOnly 14 pages are availabe for public view
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Abstract
H
epatocellular carcinoma (HCC) is the most common primary liver cancer. It is the second most common cause of cancer deaths. Globally it is the fifth most common cancer accounting for 9.1 % of global cancer. In Egypt; according to Cancer Pathology Registry (Pathology Department, Ain Shams University) HCC accounted for (88.3%) of the primary liver tumors and (45.84%) based on the Cancer Pathology Registry (National Cancer Institute, Cairo University).
The majority of HCCs arise in chronically diseased livers with or without cirrhosis. Hepatocarcinogenesis is a multistep process. Several benign lesions might be found in a cirrhotic background along with hepatocellular carcinoma (HCC), and may exhibit typical or atypical imaging features.
However, histopathological distinction can be challenging, particularly when the diagnostic material is limited and when well differentiated HCC is considered despite the variety of tumor markers that have been studied in HCC this of crucial clinical importance in determining appropriate therapy and assessing the prognosis.
The aim of our work is to study the immuno-histochemical expression of Aldoketoreductase family 1B10 (AKR1B10) in hepatocellular carcinoma and benign hepatic lesions, to assess its role in the diagnosis of hepatocellular carcinoma and in differentiating it from different benign hepatic lesions.
This study included (217) cases.120 cases were received at the Pathology department Ain Shams (Al-Demerdash) Hospital and Ain-Shams University Specialized Hospital during the period (2009-2014) and 98 cases were received at Pathology department, National Liver Institute, Menoufia University during the period (2007-2014). The following categorized groups were assigned : group (A) (n=109) cases of HCC T), group (B) (n=80) cases of corresponding near by non-tumorous tissue (NT) with or without cirrhosis both in the (TMA), group (C)(n=6)cases of Focl nodular hyperplasia (FNH) in the form of whole tissue section (WTS), group (D) (n=6) cases Hepatocellular adenoma (HCA) in the form of (WTS), group (E) (n=16) cases of Hepatic Cirrhosis without HCC.
We also evaluated the role of immunohistochemical diagnostic markers used for HCC; Heat Shock Protein 70 (HSP70), glypican 3 (GPC3) and Glutamine Synthesize (GS) alone or together with AKR1B10 or different combination panels with high accuracy for better indices.
Optimization of IHC assay using various HCC cell lines was done on Western blotting with results comparison and analysis using data on COSMIC
AKR1B10 showed highest accuracy and relatively high specificity and sensitivity in the differentiation between HCC (T) and (NT) in comparison to the studied markers. The clinicopathological relation of the AKR1B10 expression with the tumor grade was inversely related. Level of m RNA- AKR1B10 was seen higher in HCC than NT and goes in agreement with IHC.
The lowest specificity, sensitivity and accuracy was observed with the GPC3 expression.AKR1B10 recorded the highest specificity & accuracy among the tested antibodies in the distinction between HCC and (FNH&HCA).Combined usage of marker panel (AKR1B10-HSP70-GPC3-GS) regardless of which in the differentiation between HCC&NT showed better reproducibility in the combination of at least two markers to be positive. Highest specificity yield when all four markers were positive with highest sensitivity when at least one marker was positive regardless of which.
Combination of AKR1B10-HSP70 in the distinction between HCC & NT showed highest specificity if both or either was positive and accuracy seen highest when either was positive. Sensitivity was higher when either was positive. Highest sensitivity was seen in AKR1B10-GS combination when both were positive.
Combined usage of marker panel (AKR1B10-HSP70-GPC3-GS) regardless of which in the differentiation between HCC vs (FNH &HCA); showed better reproducibility in combination when at least three markers were positive. The highest sensitivity seen when at least one marker was positive regardless of which combination of AK1B10-HSP70 in the distinction between HCC & (FNH &HCA) showed highest specificity if both were positive or either. Sensitivity was higher when either was positive but a highest sensitivity was seen in the AKR1B10-GS combination of when both were positive.