Results of Immunohistochemistry in the Differential Diagnosis of Early Hepatocellular Carcinoma and Nodules With High-Grade Dysplasia in Patients With Cirrhosis

Abstract

BACKGROUND: Hepatocellular carcinoma (HCC) is the most frequent primary cancer of the liver and cirrhosis is considered a pre-malignant disease. In this context, the evolutionary sequence from low grade dysplastic nodule and high grade dysplastic nodule (HGDN) to early HCC and advanced HCC has been studied. The differential diagnosis between HGDN and early HCC is still a challenge, especially in needle biopsies OBJECTIVE: To evaluate an immunohistochemistry panel to differentiate dysplastic nodules and HCC. METHODS: Patients with cirrhosis who underwent surgical resection or liver transplantation were included. The sensitivity, specificity and accuracy for the diagnosis of neoplasia were analyzed by evaluating five markers: heat shock protein 70, glypican 3, glutamine synthetase, clathrin heavy chain and beta-catenin. P≤0.05 was considered statistically significant. RESULTS: One hundred and fifty-six nodules were included; of these, 57 were HCC, 14 HGDN, 18 low grade dysplastic nodules and 67 regenerative macronodules. Sensitivity of HCC diagnosis was 64.9% for glypican 3 and 77.2% for glutamine syntetase, while specificity was 96.0% and 96.0% respectively. When the panel of four markers was considered (excluding beta catenin), the specificity ranged from 87.9% for one positive marker to 100% for at least three markers. The best accuracy for HCC diagnosis was obtained with at least two positive markers, which was associated with a sensitivity of 82.5% and specificity of 99%. CONCLUSION: Differential diagnosis of dysplastic nodules and HCC by morphological criteria can be challenging. Immunomarkers are useful and should be used for the differential diagnosis between HCC and HGDN.

Glutamine metabolic reprogramming in hepatocellular carcinoma

“…Glutamine synthetase could distinguish atypical nodules, early diagnosis, and invasion of HCC. For instance, GS is considered to have high specificity and sensitivity to the differential diagnosis of HCC and dysplastic nodules ( Coral et al, 2021 ). Glypican-3, heat shock protein 70, and GS are utilized to distinguish a <2 cm hepatocellular lesion without classic radiological characters of HCC with cirrhosis by immunochemistry (IHC) or designed RNA probes ( Tremosini et al, 2012 ; Di Tommaso and Roncalli, 2017 ; Bakheet et al, 2020 ).…”

Current Concepts of Precancerous Lesions of Hepatocellular Carcinoma: Recent Progress in Diagnosis

“…GPC3 is a carcinoembryonic antigen, a member of the phosphatidylinositol proteoglycan family of membrane-bound acetylated heparan sulfate proteoglycans, expressed in fetal liver and progenitor cells as well as in many HCC cases and other tissues [ 33 ]. According to a study by Coral et al, GPC3 has a sensitivity of approximately 65% and a specificity of 96% for diagnosing HCC [ 3 ]. Immunohistochemistry and a real-time reverse transcription-polymerase chain reaction showed that the expression levels of GPC3 were much greater in small HCC than in cirrhosis and other categories of minor lesions.…”

“…Precancerous lesions are characterized by a multistep process ranging from dysplastic nodule (DN) to early HCC and finally to advanced HCC [ 2 ]. Cirrhosis was considered a precancerous condition associated with a high probability of developing HCC [ 3 ]. Although liver transplantation, ablation, and surgical resection have achieved good 5-year survival rates in the treatment of early-stage HCC, only about 20% of patients with HCC are diagnosed in the very early and early stages.…”

Preneoplastic lesions in the liver: Molecular insights and relevance for clinical practice

“…43,44 The addition of the fourth marker to this panel, that is clathrin heavy chain (CHC), was associated with a gain in sensitivity and specificity for the diagnosis of early-HCC from DNs in liver biopsy. 45,46 The angiogenic markers CD34, CD31 and CD105 improve the assessment of tumour neovascularization, a surrogate marker of malignant transformation in HCC. 6,47 However, the gradual increase in their expression between HGDNs, early-HCCs and well-differentiated HCCs, limits its power of discrimination.…”

“…The overall sensitivity and specificity for the diagnosis of early‐HCC of at least two markers being positive were 70% and 100%, respectively 43,44 . The addition of the fourth marker to this panel, that is clathrin heavy chain (CHC), was associated with a gain in sensitivity and specificity for the diagnosis of early‐HCC from DNs in liver biopsy 45,46 …”