Distinction of Hepatocellular Carcinoma From Benign Hepatic Mimickers Using Glypican-3 and CD34 Immunohistochemistry

ArticleinAmerican Journal of Surgical Pathology 32(3):433-44 · April 2008with42 Reads
DOI: 10.1097/PAS.0b013e318158142f · Source: PubMed
Abstract
Distinguishing a well-differentiated hepatocellular carcinoma (HCC) from normal and cirrhotic liver tissue or benign liver nodules, such as hepatic adenoma (HA) and focal nodular hyperplasia (FNH), may be very difficult in some cases, particularly in small needle core biopsies. We studied the expression of Glypican-3 (GPC3) and CD34 in 107 cases of HCC, 19 cases of HA, and 16 cases of focal nodular hyperplasia (FNH). In addition, we studied GPC3 expression in 225 cases of nonhepatic human tumors with epithelial differentiation. Ninety-four of 107 cases (88%) of HCC showed focal or diffuse cytoplasmic GPC3 staining, whereas all HA and FNH cases were GPC3-negative, and only 7 of 225 cases (3%) of nonhepatic tumors with epithelial differentiation expressed GPC3. The sensitivity and specificity of GPC3 for HCC was 88% and 97%, respectively. There were three CD34 staining patterns observed in hepatic tissue: negative, incomplete positive, and complete positive. In negative staining pattern, only blood vessels in portal triads or rare sinusoidal spaces immediately adjacent to portal tracts were positive. The negative staining pattern was seen in normal or cirrhotic liver tissue only. The complete CD34 staining pattern showed virtually all sinusoidal spaces with CD34-positive staining throughout the lesion. The complete CD34 staining pattern was seen in virtually all cases of HCC and in only some cases of HA and FNH. The incomplete CD34 staining pattern was characterized by either CD34 positivity in virtually all sinusoidal spaces in some but not all nodules or CD34 positivity in the peripheral sinusoidal spaces adjacent to portal triads. The incomplete CD34 staining pattern was seen in rare cases of HCC and in most cases of HA and FNH. We conclude that GPC3 is a very specific marker not only for differentiating HCC from nonhepatic tumors with epithelial differentiation, but also for differentiating HCC from HA and FNH. GPC3 immunoreactivity, in combination with a complete CD34 immunostaining pattern, greatly facilitates the accuracy of distinguishing between malignant hepatic lesions and benign mimickers.
    • "A recent study showed that GPC3 is more sensitive than HepPar1 in detecting HCC [45]. It is especially useful in distinguishing hepatic adenomas or high-grate dysplastic nodules from well-differentiated HCC, in noncirrhotic patients with advanced HCC [20, 43,[46][47][48]. Firstly, germline GPC3 mutations have been found in patients with Simpson-Golabi-Behmel syndrome, [31,[49][50][51][52][53]. "
    Article · Sep 2016
    • "HCC has been widely recognized to be a highly vascular tumor, and the degree and density of vascularity has been associated with grade and aggressiveness of the tumor as well as the presence and extent of metastasis [23][24][25][26][27][28]. Several investigators have introduced methods to express in a semi-quantitative manner the degree or extent of microvessel formation (venules and capillaries) in HCC and other tumors using biomarkers such as CD34, CD105 and von Willebrand factor to assign numerical values to microvessel expression [29][30][31][32][33]. Since it has been shown that CAPERα is involved in alternative splicing of VEGF mRNA and changes in ratios of alternatively spliced VEGF isoforms lead to increased or decreased microvessel formation [8, 10], we examined microvessel density in HCC and normal liver using CD34 expression in microvessels as the surrogate marker. "
    [Show abstract] [Hide abstract] ABSTRACT: Purpose CAPERα, a tumor-associated antigen, was identified from a cDNA clone with autoantibody from a patient with hepatocellular carcinoma (HCC). It has been implicated, by way of alternative splicing of VEGF pre-mRNA, in the regulation of microvessel formation in Ewing's sarcoma. In this study, we looked for possible association of alterations in CAPERα with microvessel density in HCC. Methods Enzyme-linked immunosorbent assay using recombinant CAPERα as antigen were used to detect antibody against CAPERα. Immunohistochemistry (IHC) on liver sections was performed to analyze expression profiles of CAPERα, VEGF and CD34 in HCC and control tissues and was further used to assess the correlation of expression among CAPERα, VEGF and CD34 in HCC development. Results Autoantibody to CAPERα was highest in HCC (22/76, 28.9%), not detected in prostate cancer (0/79) and at 3.4% (3/88) in breast cancer. In immunohistochemical analysis of grades II and III HCC tissues, significantly decreased immunostaining for CAPERα was observed and this correlated directly with decreased immunostaining for VEGF (R=0.534, P=0.0003). Using CD34 immunostaining for detecting newly formed microvessels, strong staining was observed in grades II and III HCC. Normal liver sections, all of which have high expression of CAPERα were totally negative for CD34 immunostaining. A significant inverse correlation was seen between CAPERα and CD34 immunostaining (R=−0.481, P=0.0012). Conclusions Decreased expression of CAPERα appears to be correlated with appearance of microvessels. It would be of interest to elucidate the cause of altered CAPERα since new formation of microvessels is important in progression of HCC.
    Full-text · Article · Mar 2016
    • "suppressed HCC growth in vitro and in vivo, and increased the survival of HCC-bearing treated mice. The anti-tumour effect may be attributed to direct and systemic anti-tumour activities (Nagler et al., 2004). In view of our data HCC group showed significant increase in serum glypican 3 and golgi 73 levels as compared to the negative control group. Coston et al. (2008) demonstrated that the sensitivity and specificity of GPC3 for HCC was 88% and 97%, respectively. GPC3 is a very specific marker not only for differentiating HCC from non hepatic tumors with epithelial differentiation, but also for differentiating HCC from hepatic adenoma (HA) and focal nodular hyperplasia (FNH). Golgiprotein-73(GP73) is"
    [Show abstract] [Hide abstract] ABSTRACT: Background: Teucrium oliverianum and Rhazya stricta are medicinal plants used in traditional and herbal medicine for the treatment of diabetes, liver diseases and inflammatory conditions. The present study was planned to investigate the antitumor efficacy of Teucrium oliverianum and Rhazya stricta in chemically-induced hepatocellular carcinoma (HCC) in rats.Materials and Methods: Forty adult male rats weighing 170-200 g were divided into four groups; each group was comprised of ten rats: (1): Normal healthy animals served as negative control group, (2): Hepatocellular carcinoma (HCC) group in which the rats were orally administered Nnitrosodiethylamine (dissolved in 0.9% normal saline), in a dose of 20 mg/kg b.wt. five times a week for six weeks, (3): HCC group treated with Teucrium oliverianum extract in a dose of 600 mg/kg b.wt for two months and (4): HCC group treated with Rhazya stricta extract in a dose of 750 mg/kg b.wt for two months. Serum alanine aminotransferase (ALT), asparatate aminotransferase (AST), alkaline phosphatase (ALP) and gammaglutamyl transferase (γ-GT) activities were estimated. Serum carcinoembyronic antigen (CEA), alpha-fetoprotein (AFP), alpha-L-fucosidase (AFU), glypican-3 (GPC-3), golgi protein 73 (Gp-73) and vascular endothelial growth factor (VEGF) levels were determined. Histopathological examination of liver tissue sections was also carried out.Results: The HCC group showed significant elevation in serum AST, ALT, ALP and γ-GT activities as well as CEA, AFP, AFU, Gpc-3, Gp 73 and VEGF levels versus the negative control group. Photomicrograph of liver tissue sections of rats in HCC revealed hepatic parenchyma with foci of anaplastic hepatocellular carcinoma as well as other foci of cystic cholangio carcinoma associated with areas of telangictasis with haemorrhage as well as individual hepatocellular necrosis.Conclusion: Treatment of HCC groups with Teucrium oliverianum or Rhazya stricta extract experienced significant improvement in the measured biochemical parameters as well as in the structural organization of the liver. In conclusion, the current study provided experimental evidences for the antitumor efficacy of Teucrium oliverianum and Rhazya stricta against hepatocellular carcinoma. Such effect could be attributed to hepatoprotective properties, antiproliferative activity and antiangiogenic potential.
    Full-text · Article · Feb 2016
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