Diagnostic accuracy of clathrin heavy chain staining in a marker panel for the diagnosis of small hepatocellular carcinoma

Abstract

The American Association for the Study of Liver Diseases guidelines recommend the use of all available markers for improving the accuracy of the diagnosis of small hepatocellular carcinoma (HCC). To determine whether clathrin heavy chain (CHC), a novel HCC marker, is effective in combination with glypican 3 (GPC3), heat shock protein 70, and glutamine synthetase, we compared the performances of a three-marker panel (without CHC) and a four-marker panel (with CHC) in a series of small HCCs ( 2 cm) and nonsmall HCCs by core biopsy with a 20-to 21-gauge needle. The series included 39 nonsmall HCCs and 47 small HCCs (86 in all); the latter showed a well-differentiated histology [small grade 1 (G1)] in 30 cases (63.8%). The panel specificity was analyzed with the adjacent/extranodular cirrhotic liver (n 5 30) and low-grade (n 5 15) and high-grade dysplastic nodules (n 5 16) as a control group. Absolute specificity (100%) for HCC was obtained only when at least two of the markers were positive (which two markers were positive did not matter). The addition of CHC to the panel increased the diagnostic accuracy for small HCCs (from 76.9% to 84.3%), and there was an important gain in sensitivity (from 46.8% to 63.8%). The four-marker panel had lower rates of accuracy (67.4%) and sensitivity (50%) for small G1 HCCs versus nonsmall G1 HCCs (93.9% and 88.2%, respectively). In seven cases (including six small G1 HCCs), there was no staining with any of the markers. Cirrhotic control livers were stained for CHC in four cases (13.3%) and for GPC3 in one case (3.3%). Conclusion: The addition of CHC to the panel supports the diagnosis of small HCCs in challenging nodules on thin core biopsy samples. Small G1 HCCs include a group of earlier tumors characterized by a more silent phenotype and the progressive acquisition of the markers under study. The search for additional markers for early HCC diagnosis is warranted. (HEPATOLOGY 2011; 53:1549-1557 See Editorial on Page 1427 H epatocellular carcinoma (HCC) is one of the most common malignancies worldwide, and its incidence is growing in association with viral (hepatitis C virus) and nonviral (nonalcoholic steatohepatitis) chronic liver diseases. 1 HCC is a lethal cancer, and improved survival relies on the detection of small ( 2 cm) and early tumors, which are less likely to have disseminated. Radiology is the main technique used to detect HCC in the setting of cirrhosis; typical imaging shows HCCs > 2 cm in more than 90% of cases. However, when the radiological features of hepatic liver nodules in cirrhosis are not typical, the American Association for the Study of Liver Diseases (AASLD) guidelines recommend the use

Morphophenotypic changes in human multistep hepatocarcinogenesis with translational implications

“…During carcinogenesis, a change in the vascular support is a hallmark of the evolution to pHCC, which can be demonstrated by the use of endothelial markers [10] [11]. Difficult cases however are in need of a more dedicated approach, contemplating the use of a robust panel of biomarkers as that already validated (GPC3-Glypican 3, HSP70-Heat shock protein 70, GS-Glutamine synthetase) [12] [13] [14], which has absolute specificity but limited sensitivity and of markers recently suggested as diagnostically useful, such as CHC (clathrin heavy chain) [15] and EZH2 (Enhancer of zeste homologue 2) [16].…”

Recent advances in the classification of hepatocellular carcinoma

“…22 Similarly, Cai et al suggested the use of the enhancer of EZH2 (zeste homologue 2) in combination with GPC-3 and HSP-70. 23 Arginase-1, an enzyme of the urea cycle, has been shown to be more sensitive than HepPar-1 in detecting poorly differentiated HCCs.…”

Hepatocellular tumors: Immunohistochemical analyses for classification and prognostication

“…With the 4-maker panel, staining by at least 2 markers shows a diagnostic accuracy of 97% and 84.3% in non-small HCCs and small HCCs, respectively. CHC was also reported as the most single sensitive marker for small grade 1 HCC, giving a sensitivity of 58.8%, versus GS (41.2%), HSP70 (17.6%) and GPC3 (11.8%) [46] (Figure 2). Future perspectives on this topic will be the use of GPC-3 as a prognostic marker for HCC.…”

“…[46] . With the 4-maker panel, staining by at least 2 markers shows a diagnostic accuracy of 97% and 84.3% in non-small HCCs and small HCCs, respectively.…”