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International Journal of Cancer Research
Year: 2006  |  Volume: 2  |  Issue: 3  |  Page No.: 257 - 266

Immunohistological Localization of Human FAT1 (hFAT) Protein in 326 Breast Cancers. Does this Adhesion Molecule Have a Role in Pathogenesis?

Nantana Kaewpila, Gordon F. Burns and Anthony S.Y. Leong    

Abstract: The immunohistological localization of human FAT1 (hFAT) protein, a recently described member of the cadherin superfamily, was evaluated in 326 breast cancers and correlated with histologic type and grade. All tumors showed diffuse staining for hFAT. Immunoexpression of the protein was generally strong in Lobular Carcinoma in situ (LCIS, n = 2) and Ductal Carcinoma in situ (DCIS, n = 55). hFAT was also strongly immunoexpressed in all types of invasive carcinoma. Grade 3 DCIS displayed the highest hFAT intensity compared to lower grade tumors, 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 tumors showed moderate (n = 63) or strong staining (n = 49), although grade 3 IDC revealed significantly decreased immunoexpression compared to grade 1 IDC (p = 0.03). These results illustrate that hFAT1 does not display the pattern of expression seen with the E-cadherin- -catenin adhesion complex; however, its overexpression 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.

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