Dysadherin is a
cancer-associated cell membrane
glycoprotein, which downregulates
E-cadherin and promotes
metastasis. We studied the clinicopathological features in 72 cases of
epithelioid sarcoma and in six cases of malignant
rhabdoid tumor, and also assessed the immunohistochemical expression of dysadherin,
E-cadherin and MIB-1 in
epithelioid sarcoma and malignant
rhabdoid tumor cases. In addition, we compared dysadherin
mRNA expression between
epithelioid sarcoma and malignant
rhabdoid tumor cell lines, using RT-PCR and real-time quantitative RT-PCR analysis. Immunohistochemical dysadherin expression was more frequently observed in proximal-type
epithelioid sarcoma (71%) in comparison with distal-type
epithelioid sarcoma (36%) (P = 0.037). Furthermore, seven proximal-type
epithelioid sarcoma cases mimicking malignant
rhabdoid tumor (histologically classified as the large cell type, accompanied by frequent rhabdoid cells and located in deep soft tissue) were all positive for dysadherin (100%), whereas dysadherin expression was not detected at all in any of the true six malignant
rhabdoid tumors (0%). Cell lines established from proximal-type
epithelioid sarcoma revealed significantly higher levels of dysadherin
mRNA expression, compared with the levels seen in malignant
rhabdoid tumor cell lines by real-time quantitative RT-PCR (P = 0.0433).
Epithelioid sarcoma patients with dysadherin expression survived for a significantly shorter time than those without dysadherin expression (P = 0.001). In multivariate analysis, dysadherin immunopositivity (P = 0.0004) was one of the two independent adverse prognostic factors. We conclude that dysadherin expression in
epithelioid sarcoma is a significant poor prognostic factor and that it is a powerful diagnostic marker for distinguishing
epithelioid sarcoma, including the proximal-type
epithelioid sarcoma, from malignant
rhabdoid tumor. In
epithelioid sarcoma, especially in proximal-type
epithelioid sarcoma, increased cell disadhesion and motility by dysadherin plays an important role to acquire aggressive biological behavior. However, in malignant
rhabdoid tumor, cell growth cycle that is regulated by hSNF5/INI1 gene seems to be critical to lethal biological behavior rather than dysadherin.