Signet-ring cell carcinomas (SRCCs) tend to present at higher stages and thus are generally associated with a worse prognosis. It has been postulated that a deficiency of E-cadherin may be causal in the pathogenesis of SRCC in animal models. In this study, we systemically analyzed the expression of E-cadherin and â-catenin, a key component of the cadherin complex, in 137 consecutive SRCCs of various organ systems to explore the significance of these molecules in the pathogenesis and progression of SRCCs. Seventy-six percent of SRCCs showed loss or reduced E-cadherin expression. Aberrant â-catenin expression, defined as loss of membranous expression and nuclear/cytoplasmic subcellular localization, was observed in 60% of these cases, with the altered â-catenin expression observed most commonly in the breast (93%) and least in the lung (38%) primaries. Further, the aberrant â-catenin was significantly associated with pathologic nodal stage (P=0.002) and clinical stage (P=0.02). Our findings demonstrated that reduced membranous E-cadherin and aberrant â-catenin expression were frequent events in SRCCs of various organs, and that the altered â-catenin expression was significantly associated with advanced disease. The observations further support the importance of these molecules in the pathogenesis of SRCCs, and indicate the fundamental role of the Wnt/â-catenin signaling pathway in the progression of these tumors. Further investigations of the downstream molecules in this cascade may provide potential novel therapeutic targets for this aggressive tumor type.
Cadherins Carcinoma, Signet Ring Cell