Prognostic value of the preserved expression of the E-cadherin and catenin families of adhesion molecules and of beta-catenin mutations in synovial sarcoma.
This study addresses the immunohistochemical expression of the E-cadherin and catenin families and mutations of the beta-catenin gene detected by PCR-SSCP in synovial sarcoma. Immunohistochemical analysis was performed for 72 cases, with follow-up data available on 62. The prognostic value of the expression of these proteins was evaluated. Reduced immunoreactivity for E-cadherin and alpha-catenin was significantly correlated with a poor survival rate (p=0.0040 and 0.0053, respectively). According to multivariate analysis, low AJC stage (stages I and II: p<0.0001), the preservation of alpha-catenin expression (p=0.0001), and a low necrotic rate (<50%: p=0.0139) were independent favourable prognostic factors. Widespread aberrant staining 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 widespread 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 performed 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-cadherin and alpha-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 levels of beta-catenin, with or without mutation, could contribute to the development and progression of synovial sarcoma, through increasing the proliferative activity of the tumour cells.
Saito
T
T
Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Oda
Y
Y
Sakamoto
A
A
Tamiya
S
S
Kinukawa
N
N
Hayashi
K
K
Iwamoto
Y
Y
Tsuneyoshi
M
M
D015820:Cadherins / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008940:Mitotic Index; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011237:Predictive Value of Tests; D011379:Prognosis; D013584:Sarcoma, Synovial / Q000378:metabolism* / Q000473:pathology; D012737:Sex Factors
D015820:Cadherins; D002352:Carrier Proteins