Prognostic significance of dysadherin expression in epithelioid sarcoma and its diagnostic utility in distinguishing epithelioid sarcoma from malignant rhabdoid tumor.
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.
Department of Anatomic Pathology, Pathological Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Teiyu
T
Izumi
Yoshinao
Y
Oda
Tadashi
T
Hasegawa
Yukihiro
Y
Nakanishi
Hiroshi
H
Iwasaki
Hiroshi
H
Sonobe
Hiroaki
H
Goto
Hidenari
H
Kusakabe
Tomonari
T
Takahira
Chikashi
C
Kobayashi
Ken-Ichi
K
Kawaguchi
Tsuyoshi
T
Saito
Hidetaka
H
Yamamoto
Sadafumi
S
Tamiya
Yukihide
Y
Iwamoto
Masazumi
M
Tsuneyoshi
D014408:Biomarkers, Tumor / Q000378:metabolism; D001859:Bone Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D002452:Cell Count; D045744:Cell Line, Tumor; D003937:Diagnosis, Differential; D005260:Female; D019085:Fluorescent Antibody Technique, Direct; D015870:Gene Expression; D006801:Humans; D007124:Immunoenzyme Techniques; D007473:Ion Channels; D007564:Japan / Q000453:epidemiology; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D008840:Microfilament Proteins; D008940:Mitotic Index; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000032:analysis; D018335:Rhabdoid Tumor / Q000378:metabolism / Q000473:pathology*; D012509:Sarcoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D012983:Soft Tissue Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D015996:Survival Rate
D014408:Biomarkers, Tumor; C451410:FXYD5 protein, human; D007473:Ion Channels; D008562:Membrane Glycoproteins; D008840:Microfilament Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm