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S‐100‐positive nerve fibers in hepatocellular carcinoma and intrahepatic cholangiocarcinoma: An immunohistochemical study

The aim of the present study was to determine whether or not liver carcinomas are innervated, since there have been no previous reports on the distribution of nerve fibers in human hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). We investigated nerve fibers by immunohistochemical and morphometric methods in 63 cases of HCC and 28 cases of ICC. An antibody to S‐100 protein was used to visualize nerve fibers. In HCC, S‐100‐positive nerve fibers were absent in the tumoral region, including the sinusoids, and tumoral fibrous septa, while in the capsule of HCC some S100‐positive nerve fibers (density: 0.08 ± 0.03/mm2) were present in contact with vasculatures. In ICC, a few nerve fibers were noted in the tumoral stroma (density: 0.02 ± 0.01/mm2). No nerve fibers were seen in the neovasculized vessels (tumor vessels) in both HCC and ICC. In invasive regions of HCC and ICC, there were S‐100‐positive nerve fibers in pre‐existing residual portal tracts (density: HCC, 0.11 ± 0.03/mm2; ICC, 0.13 ± 0.04/mm2). In non‐tumor regions of HCC and ICC, there were many S100‐positive nerve fibers (density: 0.41 ± 0.13/mm2) in portal tracts and, to a much lesser degree, in the sinusoids. These results suggest that tumor cells and vasculatures in HCC and ICC are rarely influenced by nerve fibers.