Expression of frizzled-related protein and Wnt-signalling molecules in invasive human breast tumours

Frizzled‐related protein (Frp) is a new family of secreted proteins that contain a region homologous to the extracellular cysteine‐rich domain (CRD) of the frizzled family proteins. The role of Frp protein is far from clear. To explore the role of Frp and its relationship to the Wnt‐signalling pathway in breast cancer, in situ hybridization and immunohistochemical analyses of Frp, Wnt‐1, APC, β‐catenin, and its target genes c‐myc and cyclin D1 were conducted in 70 specimens of invasive ductal carcinomas of the human breast. Frp mRNA was down‐regulated in 62 and elevated in eight tumour specimens, compared with adjacent normal tissues. In the course of tumour progression, however, Frp mRNA steadily increased in both tumour and the adjacent tissues. Interestingly, the number of cases with axillary lymph node metastasis was significantly lower in the group with elevated Frp than in the group with decreased Frp, suggesting that Frp may contribute as a prognostic factor in invasive breast cancer. Wnt‐1, a gene implicated in human breast cancer, was markedly elevated in grade 1 tumours, but declined as tumour grade declined. The level of Wnt‐1 was linearly correlated with its downstream target β‐catenin (p