Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver cancer. Currently, there is limited knowledge of neoplastic transformation of hepatocytes in HCC. In clinical practice, the high rate of HCC local recurrence suggests the presence of different hepatocyte populations within the liver and particularly in the tumor proximity. The present study investigated primary human hepatocyte cultures obtained from liver specimens of patients affected by cirrhosis and HCC, their proliferation and transformation. Liver samples were obtained from seven HCC cirrhotic patients and from three patients with normal liver (NL). Immediately after surgery, cell outgrowth and primary cultures were obtained from the HCC lesion, the cirrhotic tissue proximal (CP, 1-3 cm) and distal (CD, >5 cm) to the margin of the neoplastic lesion, or from NL. Cells were kept in culture for 16 weeks. Morphologic analyses were performed and proliferation rate of the different cell populations compared over time. Glypican-3, Heppar1, Arginase1 and CD-44 positivity were tested. The degree of invasiveness of cells acquiring neoplastic characteristics was studied with a transwell migration assay. We observed that HCC cells maintained their morphology and unmodified neoplastic characteristics when cultured. Cells isolated from CP, showed a progressive morphologic transformation in HCC-like cells accompanied by modification of markers expression with signs of invasiveness. Absence of HCC contamination in the CP isolates was confirmed. In CD samples some of these characteristics were present and at significantly lower levels. With the present study, we are the first to have identified and describe the existence of human hepatocytes near the cancerous lesion that can transform in HCC in vitro.
Highlights
Hepatocellular carcinoma (HCC) is the most common primary liver cancer (85-90%)
Each specimen (NL, cirrhotic distal (CD), cirrhotic proximal (CP) and HCC) used to obtain primary cultures was evaluated for GPC3, Arginase1, and hepatocytes paraffin1 (Heppar1) expression
With the present study we demonstrated for the first time that hepatocytes obtained from proximal areas to HCC present morphologic and neoplastic transformation when cultured in vitro
Summary
Hepatocellular carcinoma (HCC) is the most common primary liver cancer (85-90%). It is estimated that 8,000‐11,000 new cases of HCC occur annually in the United States and this number is increasing every year. HCC is responsible for half million deaths annually (7.9% of all cancers) and is the third leading cause of cancer-related mortality worldwide [1,2,3]. The effective treatments of HCC are liver transplantation (LTX), surgical resection or loco regional ablative therapy [4,5,6]. While surgical treatments remove some of the cirrhotic tissue surrounding the tumor, the other ablative therapies focus on the destruction of cancerous tissue alone. The current clinical practice requires obtaining at least 1 cm margin from peri-neoplastic cirrhotic tissue to avoid missing tumor cells or satellite micro-foci in order to obtain a radical oncologic extirpation. Despite the 5-year disease-free survival rates of ~70%, up to 78% of local recurrence rate has been reported [5,6]
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.
