Enhancer of zeste homologue 2 (EZH2) is a reliable immunohistochemical marker to differentiate malignant and benign hepatic tumors

Abstract

BackgroundThe immunohistochemical demonstration of Enhancer of zeste homologue 2 (EZH2) proved to be a useful marker in several tumor types. It has been described to distinguish reliably hepatocellular carcinomas from liver adenomas and other benign hepatocellular lesions. However, no other types of malignant liver tumors were studied so far.MethodsTo evaluate the diagnostic value of this protein in hepatic tumors we have investigated the presence of EZH2 by immunohistochemistry in hepatocellular carcinomas and other common hepatic tumors.EZH2 expression was examined in 44 hepatocellular carcinomas, 23 cholangiocarcinomas, 31 hepatoblastomas, 16 other childhood tumor types (rhabdomyosarcoma, neuroblastoma, Wilms’ tumor and rhabdoid tumor), 17 metastatic liver tumors 24 hepatocellular adenomas, 15 high grade dysplastic nodules, 3 biliary cystadenomas, 3 biliary hamartomas and 3 Caroli’s diseases.ResultsMost of the malignant liver tumors were positive for EZH2, but neither of the adenomas, cirrhotic/dysplastic nodules, reactive and hamartomatous biliary ductules stained positively.ConclusionsOur immunostainings confirm that EZH2 is a sensitive marker of hepatocellular carcinoma, but its specificity is very low, since almost all the investigated malignant liver tumors were positive regardless of their histogenesis. Based on these results EZH2 is a sensitive marker of malignancy in hepatic tumors. In routine surgical pathology EZH2 could be most helpful to diagnose cholangiocarcinomas, because as far as we know this is the first marker to distinguish transformed and reactive biliary structures. Although hepatoblastomas also express EZH2, the diagnostic significance of this observation seems to be quite limited whereas, the structurally similar, other blastic childhood tumors are also positive.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1173195902735693

Immunohistochemical Study of Glypican-3 and HepPar-1 in Differentiating Hepatocellular Carcinoma from Metastatic Carcinomas in FNA of the Liver

“…Recently new immunohistochemical markers such as Arginase-1 (Arg-1) which is recognized as a potential marker for hepatocellullar differentiation [15], and enhancer of zeste homologue 2(EZH2) which is reliable marker for HCC compared to non-malignant hepatocellular lesions [16] .…”

The importance of EZH2 and MOC‐31 expression in the differential diagnosis of benign and malignant effusions

“…8 While approximately 67% of malignant effusions can be diagnosed with smear preparations, this rate can be increased to 83-85% by applying various immunohistochemical (IHC) markers to the cell blocks. [17][18][19][20] Furthermore, overexpression of EZH2 is associated with proliferation, progression and aggressive behavior of the tumor. [1][2][3][9][10][11] These markers have been used in panels in different combinations in many studies.…”

From large to small: the immunohistochemical panel in the diagnosis of early hepatocellular carcinoma

“…In the present study, we wanted to validate the panel of markers GS–GPC3–HSP70–together with EZH2–in a representative setting of 100 liver nodules (among which 75 were <20 mm). They were evaluated in both surgical specimens and in the corresponding ‘backtable’ biopsies, in order to simulate a diagnostic path in a real setting, and thus to verify the actual diagnostic sensitivity for each marker in needle biopsies.…”

“…Later, these three markers were suggested as diagnostic criteria for eHCC in the 2010 World Health Organisation edition and by the EASL guidelines, later revised by the Barcelona group . More recently, enhancer of zeste homologue 2 (EZH2) was proposed–outside of the guidelines–in combination with the other three markers . In order to increase the sensitivity of IHC evaluation for eHCC diagnosis, the International Consensus Group suggested considering as diagnostic for eHCC the positivity of at least two markers .…”