Reduced expression of plakoglobin correlates with adverse outcome in patients with neuroblastoma

Plakoglobin and its homologue beta -catenin are cytoplasmic proteins that m ediate adhesive functions by interacting with cadherin receptors and signal ing activities by interacting with transcription factors. It has been sugge sted that plakoglobin can suppress tumorigenicity whereas beta -catenin can act as an oncogene. We investigated the correlation between the expression pattern of N-cadherin, beta -catenin, and plakoglobin and tumor behavior i n primary tumors of 20 neuroblastoma patients of all stages and in 11 human neuroblastoma cell lines. N-cadherin and beta -catenin were detected in 9 of 11 and 11 of 11 cell lines, respectively, whereas plakoglobin was undete ctable or severely reduced in 6 of 11 cell lines. Tumor cells from 16 of 20 patients expressed N-cadherin and 20 of 20 patients expressed beta -cateni n at levels similar to those of normal ganglion cells. Plakoglobin was unde tectable in 9 of 20 tumors. Plakoglobin deficiency in the primary tumors wa s significantly associated with adverse clinical outcome. Five of the patie nts with plakoglobin-negative tumors died whereas four patients are alive w ithout evident disease. In contrast, all patients with plakoglobin-positive tumors are alive; 2 of 11 are alive with the disease and 9 of 11 are alive without evident disease. These results suggest that down-regulation of pla koglobin may be of prognostic value for neuroblastoma patients as predictor of poor outcome.