Immunohistological localisation of human FAT1 (hFAT) protein in 326 breast cancers. Does this adhesion molecule have a role in pathogenesis?

Aims: To examine the immunohistological expression in human breast cancers of human FAT1 (hFAT) protein, a recently described member of the cadherin superfamily, and its correlation with histological type and grade. Methods: A total of 326 cases of invasive and in situ breast cancer representing a broad spectrum of histological subtypes were immunostained with affinity-purified rabbit antibodies produced to the cytoplasmic region of hFAT using a standard avidin - biotin system. Staining intensity was arbitrarily graded on a scale of 0 to 3. Results: All tumours showed diffuse staining for hFAT. Immunoexpression of the protein was generally strong in both lobular (LCIS, n=2) and ductal in situ carcinoma ( DCIS, n=55). hFAT was also strongly immunoexpressed in all types of invasive carcinoma. Grade 3 DCIS displayed the highest hFAT intensity compared with lower grade tumours, with significant differences between grade 1 and 3 ( p=0.015) and grade 2 and 3 ( p=0.047). With invasive ductal carcinomas ( n=128) the difference was not as clear-cut, as most tumours showed moderate ( n=63) or strong staining ( n=49), although grade 3 IDC revealed significantly decreased immunoexpression compared with grade 1 IDC (p=0.03). Conclusions: The results illustrate that hFAT1 does not display the pattern of expression seen with the E-cadherin-beta-catenin adhesion complex; however, its over-expression and diffuse expression in both in situ and invasive carcinoma strongly suggests a role in carcinogenesis. From the known functions of FAT1 it is suggested that the concurrent loss of classical cadherins from cell-cell junctions accompanied by increased FAT1 expression contributes to loss of duct formation, and increased cell migration and invasion.