Diagnostic value of clusterin immunostaining in hepatocellular carcinoma

Abstract Background Histologic distinction between well differentiated hepatocellular carcinoma (HCC) and benign hepatocellular mass lesions is a known challenge. Existing biomarkers are of limited diagnostic value. Our previous studies observed an enhanced canalicular expression pattern of clusteri...

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Main Authors: Yuan Li, Fangfang Liu, Wendi Zhou, Sharon Zhang, Peiguo Chu, Fan Lin, Hanlin L. Wang
Format: Article
Language:English
Published: BMC 2020-10-01
Series:Diagnostic Pathology
Subjects:
Online Access:http://link.springer.com/article/10.1186/s13000-020-01041-8
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author Yuan Li
Fangfang Liu
Wendi Zhou
Sharon Zhang
Peiguo Chu
Fan Lin
Hanlin L. Wang
author_facet Yuan Li
Fangfang Liu
Wendi Zhou
Sharon Zhang
Peiguo Chu
Fan Lin
Hanlin L. Wang
author_sort Yuan Li
collection DOAJ
description Abstract Background Histologic distinction between well differentiated hepatocellular carcinoma (HCC) and benign hepatocellular mass lesions is a known challenge. Existing biomarkers are of limited diagnostic value. Our previous studies observed an enhanced canalicular expression pattern of clusterin (CLU) in HCC, which was not observed in benign hepatocellular mass lesions such as hepatocellular adenoma. The aim of this study was to further investigate its diagnostic value for HCC by examining the expression pattern of CLU in a large number of non-hepatocellular tumors, and by comparing it with two other commonly used hepatocellular markers pCEA and CD10 that also show a canalicular staining pattern in HCC. Methods Enhanced canalicular staining patterns of CLU, pCEA and CD10 were analyzed on 54 surgically resected well to moderately differentiated HCCs on whole tissue sections, of which 37 had surrounding regenerative nodules while the remaining 17 had a non-cirrhotic background. CLU immunostaining was also performed on tissue microarray sections that contained 74 HCCs (40 of which were also stained for pCEA and CD10), 55 normal liver tissue samples, and 1305 non-hepatocellular tumors from multiple organs. Results Enhanced CLU canalicular staining was observed in 70% (89/128) HCCs but not in regenerative nodules, normal liver tissues or any non-hepatocellular tumors. The sensitivity and specificity for enhanced canalicular staining pattern of CLU in HCCs were 0.70 and 1.00. This enhanced canalicular pattern was observed in only 26 and 23% HCCs for CD10 and pCEA, respectively. These results further demonstrate that the distinctive enhanced canalicular pattern of CLU is unique to HCC. Conclusions CLU is superior to pCEA and CD10 as a diagnostic immunomarker in that it can help distinguish well to moderately differentiated HCC not only from non-HCC malignancies but also from benign hepatocellular mass lesions.
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spelling doaj.art-23defe78090c4ceb96829b15566d24522022-12-22T01:04:38ZengBMCDiagnostic Pathology1746-15962020-10-011511710.1186/s13000-020-01041-8Diagnostic value of clusterin immunostaining in hepatocellular carcinomaYuan Li0Fangfang Liu1Wendi Zhou2Sharon Zhang3Peiguo Chu4Fan Lin5Hanlin L. Wang6Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLADepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLADepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLADepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLADepartment of Pathology, City of Hope National Medical CenterDepartment of Laboratory Medicine, Geisinger Medical CenterDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLAAbstract Background Histologic distinction between well differentiated hepatocellular carcinoma (HCC) and benign hepatocellular mass lesions is a known challenge. Existing biomarkers are of limited diagnostic value. Our previous studies observed an enhanced canalicular expression pattern of clusterin (CLU) in HCC, which was not observed in benign hepatocellular mass lesions such as hepatocellular adenoma. The aim of this study was to further investigate its diagnostic value for HCC by examining the expression pattern of CLU in a large number of non-hepatocellular tumors, and by comparing it with two other commonly used hepatocellular markers pCEA and CD10 that also show a canalicular staining pattern in HCC. Methods Enhanced canalicular staining patterns of CLU, pCEA and CD10 were analyzed on 54 surgically resected well to moderately differentiated HCCs on whole tissue sections, of which 37 had surrounding regenerative nodules while the remaining 17 had a non-cirrhotic background. CLU immunostaining was also performed on tissue microarray sections that contained 74 HCCs (40 of which were also stained for pCEA and CD10), 55 normal liver tissue samples, and 1305 non-hepatocellular tumors from multiple organs. Results Enhanced CLU canalicular staining was observed in 70% (89/128) HCCs but not in regenerative nodules, normal liver tissues or any non-hepatocellular tumors. The sensitivity and specificity for enhanced canalicular staining pattern of CLU in HCCs were 0.70 and 1.00. This enhanced canalicular pattern was observed in only 26 and 23% HCCs for CD10 and pCEA, respectively. These results further demonstrate that the distinctive enhanced canalicular pattern of CLU is unique to HCC. Conclusions CLU is superior to pCEA and CD10 as a diagnostic immunomarker in that it can help distinguish well to moderately differentiated HCC not only from non-HCC malignancies but also from benign hepatocellular mass lesions.http://link.springer.com/article/10.1186/s13000-020-01041-8ClusterinpCEACD10Hepatocellular carcinomaImmunohistochemistry
spellingShingle Yuan Li
Fangfang Liu
Wendi Zhou
Sharon Zhang
Peiguo Chu
Fan Lin
Hanlin L. Wang
Diagnostic value of clusterin immunostaining in hepatocellular carcinoma
Diagnostic Pathology
Clusterin
pCEA
CD10
Hepatocellular carcinoma
Immunohistochemistry
title Diagnostic value of clusterin immunostaining in hepatocellular carcinoma
title_full Diagnostic value of clusterin immunostaining in hepatocellular carcinoma
title_fullStr Diagnostic value of clusterin immunostaining in hepatocellular carcinoma
title_full_unstemmed Diagnostic value of clusterin immunostaining in hepatocellular carcinoma
title_short Diagnostic value of clusterin immunostaining in hepatocellular carcinoma
title_sort diagnostic value of clusterin immunostaining in hepatocellular carcinoma
topic Clusterin
pCEA
CD10
Hepatocellular carcinoma
Immunohistochemistry
url http://link.springer.com/article/10.1186/s13000-020-01041-8
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