Quantitative evaluation of lysozyme- and CD68-positive Kupffer cells in diethylnitrosamine-induced hepatocellular carcinomas in monkeys.

Quantitative analysis of lysozyme- and CD68-positive Kupffer cells was carried out in connection with diethylnitrosamine-induced hepatocarcinogenesis in non-human primates. The number of Kupffer cells/mm2 was determined in 28 cases of hepatocellular carcinoma (HCC) and seven age-matched controls. The Kupffer cell counts (mean +/-SEM) gradually decreased in the following order, irrespective of the histochemical markers (lysozyme or CD 68) used: healthy control liver (101.7 +/- 13.5 and 103.2 +/- 11.9 respectively), non-cirrhotic and non-neoplastic host liver (54.3 +/- 13.6 and 50.5 +/- 15.4), cirrhotic host liver (26.2 +/- 8.2 and 27.2 +/- 3.3), HCC tissue (20.7 +/- 4.4 and 19.3 +/- 4.1) and metastatic foci in the lung (9.8 +/- 1.8 and 9.7 +/- 2.8). The difference between the normal liver and the non-neoplastic, non-cirrhotic portions of the HCC-bearing liver was significant (P < 0.05). A highly significant difference was found between the number of Kupffer cells found in healthy control or non-neoplastic liver and those found in HCC nodules (P < 0.0001 and P < 0.0005 respectively). The results obtained by hematoxylin and eosin staining and lysozyme/CD68 immunohistochemistry were highly similar, indicating that this decrease was attributable primarily to numeric loss of Kupffer cells. The results suggest that the reduction in the number of Kupffer cells in HCC is a constant feature of hepatocarcinogenesis not only in rodent models, but also in non-human primates.