Hepatocellular tumors: immunohistochemical analyses for classification and prognostication

Abstract

Following the classification of hepatocellular nodules by the International Working Party in 1995 and further elaboration by the International Consensus Group for Hepatocellular Neoplasia in 2009, entities under the spectrum of hepatocellular nodules have been better characterized. Research work hence has been done to answer questions such as distinguishing high-grade dysplastic nodules from early hepatocellular carcinoma (HCC), delineating the tumor cell origin of HCC, identifying its prognostic markers, and subtyping hepatocellular adenomas. As a result, a copious amount of data at immunohistochemical and molecular levels has emerged. A panel of immunohistochemical markers including glypican-3, heat shock protein 70 and glutamine synthetase has been found to be of use in the diagnosis of small, well differentiated hepatocellular tumors and particularly of HCC. The use of liver fatty acid binding protein (L-FABP), β-catenin, glutamine synthetase, serum amyloid protein and C-reactive protein is found to be helpful in the subtyping of hepatocellular adenomas. The role of tissue biomarkers for prognostication in HCC and the use of biomarkers in subclassifying HCC based on tumor cell origin are also discussed.

Keywords: Classification; Hepatocellular tumors; Immunohistochemical.

Figure 1

GPC-3 expression rate in various types of hepatocellular nodules (in the pooled series of 10 studies).

Figure 2

Algorithm for applying the 3-marker and 4-marker panels in the diagnosis of premalignant hepatic nodules.

Figure 3

Some immunohistochemical prognostic markers according to subcellular localization of the molecules.