Expression of cell adhesion molecules in oesophageal carcinoma and its prognostic value

Abstract

Oesophageal carcinoma remains a disease of poor prognosis. Surgical cure rates are compromised by the fact that most patients are diagnosed at a late stage of disease because of the delayed onset of symptoms, by which time metastases and organ infiltration may have already occurred. Thus, invasion and metastases play a key role in influencing patient survival, and the search for novel treatments may therefore hinge on gaining insight into the mechanisms controlling these processes. It has been established that the initial step in the metastatic cascade is the detachment of tumour cells from the primary tumour via dysregulation of normal cell-cell and cell-matrix interactions. Distinct proteins known as cell adhesion molecules (CAMs) mediate these interactions. In recent years, a plethora of information has contributed to the in depth understanding of these molecules. This review provides a brief description of five families of CAMs (cadherins, integrins, CD44, immunoglobulin superfamily, and selectins) and highlights their altered expression in relation both to prognosis and tumour behaviour in squamous cell carcinoma and adenocarcinoma of the oesophagus.

Figure 1

Diagrammatic representation of five families of cell adhesion molecules (CAMS): cadherins, integrins, CD44, immunoglobulin (Ig) CAMs, and selectins. Cadherin dimers engage in calcium dependent homotypic binding to dimers from an adjacent cell. The cytoplasmic domain of E-cadherin is complexed with β/γ catenin, which in turn is linked with the actin cytoskeleton via α catenin. Integrins are heterodimers consisting of α and β subunits that bind to extracellular molecules. The CD44 standard isoform binds to hyaluronic acid; however, the inclusion of combinations of variant (v) exons alters its binding affinity for this molecule. IgCAMs are characterised by their extracellular Ig-like domains. Selectins possess an N-terminal lectin domain that binds fucosylated and sialylated carbohydrates. NCAM, neural cell adhesion molecule.

Figure 2

Expression of α catenin protein. (A) Normal squamous epithelial tissue stained for α catenin, demonstrating strong staining along the cell–cell boundaries (original magnification, ×200). (B) Immunohistochemical staining of α catenin in oesophageal squamous cell carcinoma showing reduced expression of α catenin in the infiltrating cancer cells relative to the normal tissue (original magnification, ×200).