Prognostic value of the preserved expression of the E-cadherin and cateninfamilies of adhesion molecules and of beta-catenin mutations in synovial sarcoma

This study addresses the immunohistochemical expression of the E-cadherin a nd catenin families and mutations of the beta -catenin gene detected by PCR -SSCP in synovial sarcoma. Immunohistochemical analysis was performed for 7 2 cases, with follow-up data available on 62. The prognostic value of the e xpression of these proteins was evaluated. Reduced immunoreactivity for E-c adherin and alpha -catenin was significantly correlated with a poor surviva l rate (p = 0.0040 and 0.0053, respectively). According to multivariate ana lysis, low AJC stage (stages I and II: p<0.0001), the preservation of <alph a>-catenin expression (p=0.0001), and a low necrotic rate (<50%: p=0.0139) were independent favourable prognostic factors. Widespread aberrant stainin g of <beta>-catenin protein within cytoplasm and/or nuclei was observed in 28 cases (38.9%) and was significantly correlated with poor survival (p = 0 .0122). In addition, there was a trend towards a correlation between widesp read aberrant staining of beta -catenin and the MIB-1 labelling index (p = 0.0535). Mutational analysis of exon 3 of the beta -catenin gene was perfor med for 49 cases. Nucleotide sequencing analysis revealed that four (8.2%) contained point mutations (three in codon 32, GAC to TAC; one in codon 37, TCT to TTT). Survival data were available for three out of four cases with beta -catenin mutations; two of these patients died within 1 year (died of disease at 6 and 11 months, respectively). These results suggest that E-cad herin and beta -catenin undertake important roles as intercellular adhesion molecules; their preserved expression is associated with a better overall survival rate in synovial sarcoma and may have prognostic value. Abnormal l evels of beta -catenin, with or without mutation, could contribute to the d evelopment and progression of synovial sarcoma, through increasing the prol iferative activity of the tumour cells. Copyright (C) 2000 John Wiley & Son s, Ltd.