Fas ligand expression in BRCA1-associated hereditary breast carcinoma clearly differs from that in sporadic breast carcinoma.

BRCA1-associated hereditary breast carcinomas (HBCs) are diagnosed at a younger age and are known to show biological aggressiveness such as a high histological grade, frequent aneuploidy, compared to sporadic breast carcinomas. However, results of studies on their prognosis have been controversial. We hypothesized that some factors such as a high incidence of cell death could offset the aggressiveness of BRCA1-associated HBCs, and therefore investigated Fas and Fas ligand (Fas L) expression in 19 BRCA1-associated HBCs and 56 age-adjusted control cases. Glandepithelial and myoepithelial cells in the mammary glands expressed Fas in high incidence, but all were negative for Fas L. Fas was expressed in 89.5% of BRCA1-associated HBCs and 94.4% of the controls and no significant differences could be established between the two groups. However, in 73.7% of BRCA1-associated HBCs, Fas L was clearly expressed in the infiltrating mononuclear cells, whereas this was observed in only 14.3% of the control cases and statistical significance was established between the two groups (p < 0.0001). These results strongly suggest that carcinoma cells in BRCA1-associated HBCs are more likely to be attacked by mononuclear cells via Fas L, and this may explain, at least in part, the discrepancy with respect to the prognosis. On the other hand, carcinoma cells also expressed Fas L significantly more often (p < 0.0001) in BRCA1-associated HBCs (52.6%) than in sporadic cases (3.6%). This can be considered a kind of counterattack against the mononuclear cells or, alternatively, may enhance the Fas-Fas L pathway in an autocrine/paracrine fashion. The clinical significance of Fas L expressing carcinoma cells remains to be elucidated.