Investigation of cytokine gene expression in human colorectal cancer.

RNA was extracted from 28 samples of colorectal cancer and 26 samples of adjacent normal bowel. Northern blotting analysis showed the presence of mRNA for tumor necrosis factor (TNF) in 15 of 28 cancer samples and 6 of 26 matched normal areas. In 10 patients, TNF mRNA was found only in the tumor; in 5, TNF mRNA was seen in tumor and normal areas; and in only 1 was TNF mRNA seen in the normal, but not the malignant, area. The expression of TNF mRNA was not related to the stage of disease, degree of lymphocyte infiltration, or necrosis in the tumor. Blots were reprobed for gamma-interferon, interleukin (IL) 1 alpha and beta, IL-6, and transforming growth factor beta 1 mRNA. One tumor sample was positive for IL-1 beta, and one normal sample expressed interferon gamma mRNA. All samples had transforming growth factor beta 1 mRNA, and there was no obvious difference between levels in tumor tissues or adjacent normal areas. In situ hybridization studies with a TNF riboprobe showed that TNF mRNA was only detectable in a small minority of mononuclear and predominantly stromal cells. Immunohistochemistry on sequential sections showed that CD4- and CD8-positive lymphocytes, and macrophages, were present in the stroma. An antibody to the macrophage C3b receptor identified a minority population whose distribution corresponded closely to the cells labeled with the TNF riboprobe.