Immunohistological localisation of human FAT1 (hFAT) protein in 326 breast cancers. Does this adhesion molecule have a role in pathogenesis?
OBJECTIVE
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-ss-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.
Division of Anatomical Pathology, Hunter Area Pathology Service, University of Newcastle, Newcastle, NSW, Australia.
Nantana
N
Kwaepila
Gordon
G
Burns
Anthony S-Y
AS
Leong
D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism* / Q000473:pathology; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000378:metabolism* / Q000473:pathology; D018275:Carcinoma, Lobular / Q000378:metabolism* / Q000473:pathology; D050612:Fatty Acid Transport Proteins / Q000378:metabolism*; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism*
D014408:Biomarkers, Tumor; D050612:Fatty Acid Transport Proteins; D009363:Neoplasm Proteins; C493568:SLC27A1 protein, human