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Diagnostic Discrimination of Fine Needle Aspiration Specimens of Hepatic Nodules using Immunohistochemical Expression of GPC3 and EZH2

Samah S Elbasateeny , Taiseer R Ibrahim , Abdelmonem A Hegazy  and Noha E Shaheen

The goal of the present study was to examine the immunohistochemical expression of Glypican-3 (GPC3) and Enhancer of zeste homologue 2 (EZH2) in various histological types of hepatic nodules in order to clarify their discriminatory diagnostic value. We correlated biomarkers’ expressions with the clinicopathological variables of primary liver malignancy. Biomarkers’ expression was investigated in 64 liver needle biopsies. The specimens included primary liver malignancy (57.81%), metastatic carcinomas (15.62%) and non-malignant nodules 26.56%. The expression of GPC3 was detected in 83.33% and 15.38% of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) respectively, but not expressed in any of metastatic nodules. In HCC, GPC3 was more expressed in cases with cirrhosis, large masses of tumor and high HCCs grades with statistically significant differences with P value of 0.01, 0.035 and 0.03 respectively. The EZH2 expression was detected in 91.66% of HCC, in all cases of CC and metastatic nodules and in 5.88% of non-malignant nodules. The sensitivity, specificity and diagnostic accuracy of differentiating HCCs from non-malignant nodules were 80.95%, 100% and 90.24% respectively for GPC3; and 85.71%, 95.65% and 91.89% respectively for EZH2. The sensitivity, specificity and diagnostic accuracy for differentiating HCCs from CCs were 73.33%, 90.91% and 83.78% respectively for GPC3; and 0.0%, 62.86% and 59.46% respectively for EZH2. The sensitivity, specificity and diagnostic accuracy for differentiating HCCs from metastatic nodules were 71.43%, 100% and 88.24% respectively for GPC3; and 0.0%, 68.75% and 64.71% respectively for EZH2. In conclusion, GPC3 might be used as a good biomarker for differential diagnosis of HCC from non-malignant nodules, CC and metastasis. Its overexpression might be an indication of poor HCC prognosis. On the other hand, EZH2 is not specific for HCC, but could be a reliable biomarker for discrimination of hepatic cancers compared to non-malignant nodules.