E-cadherin is a protein that serves as a molecular anchor on the surface of epithelial cells. It is a calcium-dependent adhesion molecule, meaning its function relies on the presence of calcium ions to operate effectively. This protein is encoded by the CDH1 gene and functions as the foundational component of structures that link adjacent cells together. Understanding its presence or absence is fundamental to comprehending how normal tissues maintain their structure and how certain cancers develop and spread.
Fundamental Role in Cell Structure
E-cadherin’s primary function in healthy tissue is to mediate robust cell-to-cell adhesion, acting like a form of biological glue to hold epithelial cell sheets intact. It organizes specialized structures known as adherens junctions, which are located near the apical surface of the cells. The protein extends from the cell membrane and directly links with E-cadherin molecules on a neighboring cell, creating a cohesive bond.
This physical connection is strengthened inside the cell by a complex of proteins called catenins, including alpha, beta, and p120-catenin. These catenins connect the E-cadherin molecule to the cell’s internal scaffolding, the actin cytoskeleton. This linkage provides a physical anchoring system that is necessary for maintaining the correct polarity and three-dimensional organization of epithelial tissues. By forming these strong, continuous junctions, E-cadherin prevents individual cells from separating.
The structural integrity created by E-cadherin is necessary for maintaining tissue organization. It ensures that cells within a tissue remain stationary and organized, which is a characteristic feature of healthy epithelial architecture. The presence of functional E-cadherin effectively suppresses the ability of a cell to migrate, binding it firmly within the tissue layer.
Diagnostic Relevance of E-Cadherin Status
Pathologists use the E-cadherin status of a tumor as a tool for classifying the cancer subtype. When a biopsy is taken, specialized staining techniques like immunohistochemistry (IHC) are used to visualize the protein’s presence or absence on the cell membrane. The pattern of E-cadherin expression serves as a biomarker, especially in breast cancer, where it helps distinguish between the two most common histological types.
The differential diagnosis between Invasive Ductal Carcinoma (IDC) and Invasive Lobular Carcinoma (ILC) often relies on this single protein. A strong, uniform presence of E-cadherin on the cell surface confirms the diagnosis of IDC or a ductal subtype. Conversely, the complete loss of E-cadherin staining is considered the pathognomonic feature of ILC.
Testing for E-cadherin is particularly valuable in cases where the tumor cells exhibit ambiguous or indeterminate morphology under the microscope. In this context, a negative E-cadherin stain is a highly specific marker for confirming the diagnosis of Invasive Lobular Carcinoma. This distinction is relevant because the two subtypes often display different patterns of metastasis and may have slightly different responses to systemic therapies.
E-Cadherin Positive Tumor Types
A tumor that is E-cadherin positive means the cancer cells have retained the ability to produce and correctly localize this adhesion protein on their cell surfaces. This retention results in a tumor that maintains cell-to-cell cohesion, causing the cells to grow in clusters, sheets, or glandular structures. In breast cancer, E-cadherin positivity is characteristic of Ductal Carcinoma In Situ (DCIS) and Invasive Ductal Carcinoma (IDC).
These ductal tumors typically grow in a cohesive, nest-like pattern, reflecting the preserved cell-to-cell binding provided by the E-cadherin molecules. In gastric cancer, E-cadherin positivity is commonly associated with the “intestinal type” of adenocarcinoma, which tends to be more well-differentiated. This subtype often shows a glandular, organ-like structure within the tumor mass.
The presence of E-cadherin is frequently correlated with a more favorable prognosis compared to tumors that have lost the protein. E-cadherin positive gastric cancer patients, for instance, often exhibit better overall survival rates than those with negative tumors, particularly in early-stage disease. This is because the cohesive nature of these tumors generally makes them less prone to the single-cell dissociation that facilitates early metastatic spread.
The Biological Impact of E-Cadherin Loss
The opposite scenario, an E-cadherin negative tumor, signals a fundamental change in the cancer cell’s biology. Loss of E-cadherin expression is most frequently caused by mutations in the CDH1 gene, which is a defining molecular characteristic of Invasive Lobular Carcinoma (ILC) in the breast and diffuse-type gastric cancer. This loss destabilizes the adherens junctions, causing the cells to become discohesive and lose their epithelial characteristics.
This biological shift is often described as Epithelial-Mesenchymal Transition (EMT), a process where stationary epithelial cells acquire the migratory and invasive properties of mesenchymal cells. During EMT, the cancer cells shed their molecular glue, allowing them to escape the primary tumor mass. The resulting ILC cells characteristically invade the surrounding tissue as single files, a pattern known as the “Indian file” growth.
This loss of adhesion is a primary mechanism that enables the cancer cells to disseminate and metastasize. Diffuse-type gastric cancer, which is also characterized by a profound loss of E-cadherin, is known for its highly infiltrative growth pattern and poor prognosis. The absence of this adhesion molecule allows the tumor cells to move independently, facilitating their invasion into the lymphatic and vascular systems.