Immunological and pathobiological roles of fibulin-1 in breast cancer

Fibulin- 1 ( Fbln- 1) is an immunogenic breast cancer-related glycoprotein identified by serological analysis of cDNA expression library ( SEREX) strategy. Here, we show that dendritic cells from two breast cancer patients elicited a CD4(+)- mediated T- cell response to Fbln- 1 presentation. In both patients, an antibody response to Fbln- 1 was also found. By contrast, a Fbln- 1- seronegative patient and a weakly seropositive patient demonstrated no such T- cell response. Analysis of human breast cancers for Fbln- 1 RNA and protein expression revealed the presence of Fbln- 1C and - 1D variants. Fbln- 1 was detected in the cytoplasm and at the cell surface of different human breast carcinoma cell lines. Immunohistochemical analysis of 528 archival primary breast carcinomas showed the expression of Fbln- 1 in 35% of the cases. When the immunohistochemical findings were compared against pathobiological information associated with each specimen, an inverse relationship between Fbln- 1 and cathepsin D expression was observed ( P = 0.04). Furthermore, even though long- term survival was similar between Fbln- 1-positive and - negative cases, the survival of Fbln- 1- positive cases improved when a lymphoid infiltrate was present at the tumour site. Taken together, our findings of an Fbln-1-specific immunity and the improved survival associated with Fbln- 1 expression in the presence of lymphoid infiltration point to a role of Fbln- 1 in tumour immunosurveillance.