Carcinoma-associated collagen type III and type IV immune localization and Ito cell transformation indicate tumor-related changes in sinusoids of the human liver.

The deterioration of extracellular matrix turnover is a key event in tumor progression. It has been assumed that Ito cell transformation is stimulated by tumor-derived factors. In the present study changes in the occurrence of collagen type III and IV and Ito cell transformation are described in the sinusoids of patients with malignant gastrointestinal tumors without liver metastases, and around metastatic liver tumors using routine histology, electron microscopy as well as light microscopical and ultrastructural immunohistochemistry. Dilated sinusoids filled with lymphoid cells and variable perisinusoidal fibrosis were detected light microscopically. Collagen type III and IV immune deposits were increased perisinusoidally. Ultrastructural immunohistochemistry showed increased staining in the space of Disse and around Ito and transitional cells for both types of collagen. Ito cells were transformed into transitional cells. Pit cells appeared in the inflammatory infiltrate in sinusoids. Ito cells were significantly increased in number pericentrally and periportally. It is suggested that stimuli, which can influence Ito cellular behaviour are produced by inflammatory cells in sinusoids, resident sinusoidal cells, tumor cells or by tumor stroma. It is concluded that transformed Ito cells and increased amounts of collagen type III and IV in sinusoids of patients with malignant tumors without liver metastases or around metastatic tumors may predict tumor-related alterations of liver parenchyma, which may serve as a barrier for further outgrowths of the cancer cells.