الفهرس 
PhysiologyOnly 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. It is multifactorial in etiology and complex in pathogenesis. The major risk factor for the development of HCC is liver cirrhosis. Most patients have too advanced cancer at diagnosis for curative treatment which necessitates improving early and accurate diagnosis. However, distinction of small size HCC from dysplastic nodules may be difficult by imaging criteria alone. Also distinction of well differentiated HCC from high grade dysplastic nodule (HGDN) is also difficult to be assessed in small needle biopsy.
Therefore, this study aimed to study immunohistochemical expression of SPINK1 in HCC as a diagnostic marker to differentiate HCC (especially the well differentiated grade) from non-malignant lesions.
This was a retrospective study included 179 liver specimens from patients presented with hepatocellular focal lesions and the studied cases were divided into HCC and non-malignant lesions (focal nodular hyperplasia (FNH), cirrhosis with and without HCC, hepatocellular adenoma (HCA) and normal liver tissue) groups.
The median age of HCC cases was 58 years with predominance of male gender 81.7%. Median level of serum AFP was 200ng/ml and also 94.6% of cases were positive for hepatitis viral infection. 82.7% of cases presented by single mass with median tumor size was 5 cm. 95.7% of cases were of classic HCC type and showed different grades in the same tumor with 58.1% of cases presented with pathological stage T1 and 34.4% showed microscopic vascular invasion. 75.3% of cases arouse on
top of liver cirrhosis with 44.5% of the adjacent cirrhosis showed pre-neoplastic changes.
The current study showed there was a statistical significant difference between well differentiated HCC cases and FNH cases regarding median age (P=0.01), etiology (P<0.000), median level of serum AFP (P=0.033) and adjacent non-neoplastic liver (P<0.000). Also there was a statistical difference between well differentiated HCC cases and cirrhosis without HCC cases regarding median age (P=0.002), viral etiology (P=0.036), radiologic procedure (P=0.003) with a trend of significance regarding median level of serum AFP (P=0.068).
The present study showed that all normal liver tissue (100%), HCA cases (100%) and 4/6 of FNH cases (66.7%) were negative for SPINK1 expression and in the remaining 2 FNH cases the positive cells were near to the fibrous septa. Also 82.9% of cirrhosis with and without HCC cases were negative for SPINK1 expression (40/46 of low grade regenerative nodule (LGRN), 12/17 of low grade dysplastic nodule (LGDN) and 11/13 of HGDN) and in positive cases the positive cells were localized near nodule edge and affected by the presence of cholestatic liver disease.
Furthermore, the current study demonstrated that SPINK1 was expressed in 71/93 of HCC cases (76.3%) with diagnostic validity (sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy were 76.3%, 82.6%, 82.6%, 76.3% and 79.3% respectively).
The present study showed a statistical significant difference between FNH and well differentiated HCC (WD-HCC) cases regarding mean value of SPINK1 expression (P=0.015) with a special distribution pattern of SPINK1 in FNH cases.
The current study showed that there was a highly statistical significant difference between cirrhosis with and without HCC and WD-
HCC cases regarding SPINK1 expression with low SPINK1 score in cirrhosis cases. Moreover, there was no significant difference between cirrhosis without HCC and cirrhosis adjacent to HCC regarding SPINK1 expression (P=0.180). Also there was no significant difference between LGDN and LGRN regarding SPINK1 expression (P=0.149).
The current study showed that there was a high significant difference between WD-HCC and HGDN regarding SPINK1 expression (P=0.001) with 83.3% sensitivity and 84.6% specificity.
The present study showed that positive SPINK1 expression tended to be associated with increased tumor size (P=0.055) and also high SPINK1 positive score had a trend to be associated with high serum AFP level (P=0.064). However, there was no significant difference regarding SPINK1 expression and either vascular invasion (P=0.888) or tumor grade (P=0.72).