Aberrant E-Cadherin in Lobular CA

Invasive lobular carcinoma (ILC) makes up about 10% of all invasive breast cancers. It tends to occur a little later in life than invasive ductal cancer (early 60's as opposed to mid-50's). Hormone replacement therapy after menopause may increase the risk of ILC. The size of ILC ranges from grossly inapparent lesions that may diffusely involve the breast to discrete, firm, gray-white masses with irregular borders. Frequently, it creates an ill-defined thickening or fullness in a portion of the breast which feels different than the surrounding tissue. It is also difficult to appreciate on mammograms due to its growth characteristics. Breast MRI is superior to ultrasound and mammography in visualizing the tumor. Microscopically, ILC is consists of a uniform population of small to medium-sized tumor cells that exhibit lack of cohesion. In a classical case of ILC, they grow in slender strands or single files (Indian file) or in a concentric fashion around ducts or lobules harboring lobular carcinoma-in-situ (LCIS). The background stroma is densely fibrotic and contains foci of periductal and perivenous elastosis. A lymphocytic infiltrate is frequently present. E-Cadherin in ILC: Most cases of in-situ and invasive lobular carcinoma show absence of E-Cadherin immunoreactivity. However, aberrant expression of E-Cadherin seen in about 16% of cases does not exclude the diagnosis of ILC if the H&E features are diagnostic. The lack of E-Cadherin is due to biallelic loss of expression of a tumor suppressor gene CDH1 on chromosome 16q. E-Cadherin is a calcium-dependent transmembrane protein that plays a key role in cell-cell adhesion. As a result, the tumors like ILC that lack E-Cadherin are discohesive and frequently consist of single cells infiltrating through the breast parenchyma. ILC also shows staining with HMW cytokeratin and diffuse cytoplasmic expression of p120 catenin.