Hepatic Progenitor Cells in Metastatic Liver Carcinomas

Abstract

Aims

Hepatic progenitor cells (HPCs) are activated in various liver diseases but their role in carcinomatous environment remains unknown. We aimed to identify the possible presence and topography of HPCs in liver metastases.

Methods

We examined 14 liver resection specimens for colorectal adenocarcinoma (CRC) (n=13) and anal squamous cell carcinoma (SCC) (n=1) metastases. Immunohistochemical markers of colonic (keratin 20-K20, CDX2) and squamous cell origin (p63), HPC (K19, CD56) and stem cell (CD44) markers, and the biliary marker K7 which may also highlight HPCs were applied on routinely processed tissue sections. Double immunohisto- chemistry/immunofluorescence (K7/CDX2) and confocal microscopy were used on selected sections.

Results

K7-, Κ19- and CD56-positive ductular structures were encountered within the metastatic tumour (tumour interior and periphery), and in the immediate peritumoural area. Hybrid structures composed of HPCs and metastatic adenocarcinoma cells were recognised and confirmed by double immunostaining (K7/CDX2). Carcinoma cells were also observed singly or in groups within the epithelium of interlobular bile ducts and/or ductules in portal tracts without evidence of carcinomatous infiltration and at a distance from the metastatic foci.

Conclusions

HPCs are observed at the periphery and the interior of liver metastatic carcinomas. Bile ductules and small interlobular bile ducts may attract carcinoma cells serving as potential "metastatic niche", in line with their recognised role as HPC niches in non-neoplastic liver.

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