Prognostic significance of dysadherin expression in epithelioid sarcoma and its diagnostic utility in distinguishing epithelioid sarcoma from malignant rhabdoid tumor
Prognostic significance of dysadherin expression in epithelioid sarcoma and its diagnostic utility in distinguishing epithelioid sarcoma from malignant rhabdoid tumor
复制标题
DOI：
10.1038/modpathol.3800599
复制
发表时间：
2006-06-01
期刊：
影响因子：
7.5
通讯作者：
Tsuneyoshi, Masazumi
中科院分区：
文献类型：
--
作者：
Izumi, Teiyu;Oda, Yoshinao;Tsuneyoshi, Masazumi
Dysadherin是一种与癌症相关的细胞膜糖蛋白，可下调E-钙粘蛋白并促进转移。我们研究了72例上皮样肉瘤和6例恶性横纹肌样瘤的临床病理特征，并对上皮样肉瘤和恶性横纹肌样瘤中dysadherin、E-cadherin和MIB-1的表达进行了免疫组化检测。此外，我们比较了上皮样肉瘤和恶性横纹肌样肿瘤细胞系中dysadherin mRNA的表达，采用RT-PCR和实时定量RT-PCR分析。近端型上皮样肉瘤（71%）与远端型上皮样肉瘤（36%）相比，免疫组化dysadherin表达更频繁（P = 0.037）。此外，7例模仿恶性横纹肌样瘤（组织学分类为大细胞型，伴有常见的横纹肌样细胞，位于深部软组织）的近端型上皮样肉瘤病例均为dysadherin阳性（100%），而在6例真正的恶性横纹肌样瘤中均未检测到dysadherin表达（0%）。近端型上皮样肉瘤的细胞系中发现了更高水平的dysadherin mRNA的表达，与恶性横纹肌样肿瘤细胞系中观察到的水平相比，实时定量RT-PCR（P = 0.0433）。与dysadherin表达的上皮样肉瘤患者的生存时间明显短于那些没有dysadherin表达（P = 0.001）。在多因素分析中，dysadherin免疫阳性（P = 0.0004）是两个独立的不良预后因素之一。我们的结论是，dysadherin在上皮样肉瘤的表达是一个显着的预后不良因素，它是一个强大的诊断标志物区分上皮样肉瘤，包括近端型上皮样肉瘤，恶性横纹肌样肿瘤。在上皮样肉瘤，特别是近端型上皮样肉瘤中，由dysadherin引起的细胞脱粘和运动增加在获得侵袭性生物学行为中起重要作用。然而，在恶性横纹肌样肿瘤中，由hSNF 5/INI 1基因调控的细胞生长周期似乎是致命生物学行为的关键，而不是dysadherin。
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.