Abstract
Differential diagnosis of well-differentiated hepatocellular carcinoma (WD-HCC) and high-grade dysplastic nodules (HGDNs) represents a challenge for pathologists. Several immunohistochemistry markers have been identified to distinguish hepatocellular carcinoma (HCC) from HGDNs. However, sensitivity or specificity of the individual marker is still limited. In this study, we analyzed dynamic alteration of leukemia inhibitory factor receptor (LIFR) and CD34 during hepatocarcinogenesis from dysplastic nodules to small HCC. The diagnostic performance of LIFR and CD34 combination in WD-HCC and HGDNs was investigated by logistic regression models and validated in an independent validation cohort. LIFR was decreased and CD34 was increased along with stepwise progression of hepatocarcinogenesis from low-grade dysplastic nodules (LGDNs) to small HCC. The sensitivity and specificity of the LIFR and CD34 combination for WD-HCC detection were 93.5% and 90.5%, respectively. In addition, colony formation assay was used to explore the role of LIFR in tumorigenesis. Silencing of LIFR could significantly promote colony formation of HCC cells, whereas ectopic overexpression of LIFR resulted in impaired ability of colony formation of HCC cells. These findings indicate that LIFR and CD34 combination may be used as an available differential diagnostic model for WD-HCC from HGDNs in clinical practice.
Highlights
Hepatocellular carcinoma (HCC) is the fifth most frequent cancer and the third leading cause of cancerrelated death worldwide [1, 2]
In Wurmbach’s dataset, we found that level of leukemia inhibitory factor receptor (LIFR) mRNA was significantly decreased from liver cell dysplasia to hepatocellular carcinoma with all four probes (Figure 2B)
Based on analysis of integrated optical density (IOD), we found that level of LIFR was significant lower in sHCC than that in liver cirrhosis (LC) and DN (Figure 3D, P < 0.0001)
Summary
Hepatocellular carcinoma (HCC) is the fifth most frequent cancer and the third leading cause of cancerrelated death worldwide [1, 2]. HCC classically develops on cirrhosis through a multistep process of carcinogenesis. Among precancerous lesions developed on cirrhosis, the risk of malignant transformation has been significantly increased at approximately 20% for LGDNs and 20%– 80% for HGDNs [5, 6]. Several immunohistochemistry markers, including heat shock protein 70 (HSP70), glypican 3 (GPC3), glutamine synthase (GS), CD31, and CD34, have been identified to distinguish HCC from HDGNs [7,8,9,10]. The sensitivity for distinguishing WD-sHCC from HGDNs was only 78.1% for HSP70, 59.4% for GS and 68.8% for GPC3, respectively [8]. It is urgent to identify novel and reliable immunohistochemistry markers for differential diagnosis between HGDNs and WD-sHCC
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
