FasL is more frequently expressed in liver metastases of colorectal cancerthan in matched primary carcinomas

Colorectal carcinoma cells have recently been shown to express Fas ligand ( FasL). This ligand could allow the tumour cells to evade activated tumour-i nfiltrating lymphocytes (TILs) by inducing their apoptosis and would thus p romote tumour survival and possibly metastasis formation. To test this hypo thesis in vivo we analysed the expression of Fast mRNA and protein in paire d tissue samples of normal colonic mucosa (N), primary colorectal carcinoma s (T) and their metastases (M) from a total of 21 patients by four differen t methods. Additionally, the presence and activation status of infiltrating lymphocytes, which might contribute to the total amount of Fast in the tis sue, was determined by semiquantitative reverse transcription-polymerase ch ain reaction (RT-PCR) in the same samples. The frequency of FasL detection was 30-40% in T and was 60-100% in M, depending on the sensitivity of the m ethod. Simultaneously, the amount of CD25 mRNA, used as a measure of the nu mber of activated TILs, was in 90% of patients lower in M than in T. The in creased frequency of Fast detection in liver metastases was therefore not d ue to the presence of activated TILs. We conclude that metastasizing subpop ulations of colorectal tumour cells express Fast more frequently than the p rimary carcinomas and may be able to eliminate activated TILs in vivo via F as/FasL-induced apoptosis or other hitherto unknown mechanisms.