Dysadherin is a cancer-associated cell membrane glycoprotein. Its cDNA encodes 178 amino acids, including a putative signal sequence, a potential O-glycosylated extracellular domain, a single transmembrane domain, and a short cytoplasmic tail. Dysadherin is believed to down-regulate the expression of E-cadherin, the prime mediator of cell-cell adhesion in epithelial cells, by a posttranscriptional mechanism and promote the metastasis of carcinoma cells. To evaluate the association between dysadherin expression and E-cadherin expression in thyroid carcinoma, immunostaining for dysadherin and E-cadherin was performed in 51 papillary, 10 follicular, and 31 undifferentiated carcinomas. Immunoreactivity for dysadherin, localized at cell-cell boundaries, was detected in 39 of the 51 papillary carcinomas and all 31 undifferentiated carcinomas but not in the follicular carcinomas or normal thyroid tissue controls. Dysadherin expression was significantly higher in undifferentiated carcinoma than in papillary carcinoma and follicular carcinoma and showed significant negative correlation with E-cadherin expression. The degree of dysadherin expression was significantly associated with the prognosis, occurrence of secondary undifferentiated carcinomas, size of the primary tumor, and metastasis to the regional lymph nodes and lungs. In conclusion, a process involving increased dysadherin expression may lead to an adverse clinical outcome.

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To assess the expression of a cancer-associated fibroblasts (CAFs) marker as an indicator of prognosis, we raised anti-protein gene product 9.5 (PGP9.5) monoclonal antibody against cultured fibroblasts. PGP9.5 expression in cultured normal fibroblasts was increased by transforming growth factor beta stimulation, indicating the phenotypic alteration to activated fibroblast. We immunohistochemically evaluated PGP9.5 expression with the CAFs of 110 colorectal cancer cases under T3 stage. PGP9.5 immunoreactivity in 30% or more of CAFs was defined as high PGP9.5 expression, and the other cases were considered as having low PGP9.5 expression. Patients with high PGP9.5 expression (42.7%) had significantly shorter survival and a higher incidence of recurrence than the low PGP9.5 expression group (P = .002 and P < .001, respectively). Multivariate analysis indicated PGP9.5 expression as an independent prognostic factor for overall and recurrence-free survival partly as well as lymph node metastasis. These results indicate that PGP9.5 expression in CAFs is a helpful finding to represent the overall biologic behavior of advanced colorectal cancer.

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