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Masazumi Tsuneyoshi - One of the best experts on this subject based on the ideXlab platform.
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infrequent smarcb1 ini1 gene alteration in Epithelioid Sarcoma a useful tool in distinguishing Epithelioid Sarcoma from malignant rhabdoid tumor
Human Pathology, 2009Co-Authors: Kenichi Kohashi, Teiyu Izumi, Yoshinao Oda, Hidetaka Yamamoto, Sadafumi Tamiya, Tomoaki Taguchi, Yukihide Iwamoto, Tadashi Hasegawa, Masazumi TsuneyoshiAbstract:Loss of SMARCB1/INI1 protein expression is considered useful for confirming a histologic diagnosis of malignant rhabdoid tumor. However, loss of SMARCB1/INI1 protein expression has recently been reported in other tumors as well, including a few cases of Epithelioid Sarcoma. In addition, the histopathologic differences between proximal-type Epithelioid Sarcoma and malignant rhabdoid tumor have not been conclusively defined. We analyzed SMARCB1/INI1 protein expression in 54 Epithelioid Sarcoma (proximal-type, 25; distal-type, 29) and examined alterations of the SMARCB1/INI1 gene in the cases lacking protein expression. We found that 19 (76.0%) proximal-type Epithelioid Sarcoma and 27 (93.1%) distal-type Epithelioid Sarcoma showed loss of SMARCB1/INI1 protein expression. Analysis of 39 cases with loss of protein expression revealed 4 cases (10.3%) with SMARCB1/INI1 gene alterations at the DNA level (homozygous deletion, 2; 1- or 2-bp deletion, 2) that could have induced the loss of gene products, and all 4 of these were proximal-type Epithelioid Sarcoma. Epithelioid Sarcoma was thus associated with a high frequency of loss of SMARCB1/INI1 protein expression similar to that in malignant rhabdoid tumor. However, the frequency of SMARCB1/INI1 gene alteration at the DNA level in proximal-type Epithelioid Sarcoma was significantly lower than that in malignant rhabdoid tumor. In addition, the prognosis of patients with malignant rhabdoid tumor is significantly worse than that of patients with proximal-type Epithelioid Sarcoma (P = .001). Therefore, proximal-type Epithelioid Sarcoma and malignant rhabdoid tumor are suggested to be distinctive tumors with respect to the mechanism of the loss of SMARCB1/INI1 protein expression. Analysis of alterations in the SMARCB1/INI1 gene may thus be a useful diagnostic tool to distinguish proximal-type Epithelioid Sarcoma from malignant rhabdoid tumor.
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Infrequent SMARCB1/INI1 gene alteration in Epithelioid Sarcoma: a useful tool in distinguishing Epithelioid Sarcoma from malignant rhabdoid tumor ☆
Human pathology, 2008Co-Authors: Kenichi Kohashi, Teiyu Izumi, Yoshinao Oda, Hidetaka Yamamoto, Sadafumi Tamiya, Tomoaki Taguchi, Yukihide Iwamoto, Tadashi Hasegawa, Masazumi TsuneyoshiAbstract:Loss of SMARCB1/INI1 protein expression is considered useful for confirming a histologic diagnosis of malignant rhabdoid tumor. However, loss of SMARCB1/INI1 protein expression has recently been reported in other tumors as well, including a few cases of Epithelioid Sarcoma. In addition, the histopathologic differences between proximal-type Epithelioid Sarcoma and malignant rhabdoid tumor have not been conclusively defined. We analyzed SMARCB1/INI1 protein expression in 54 Epithelioid Sarcoma (proximal-type, 25; distal-type, 29) and examined alterations of the SMARCB1/INI1 gene in the cases lacking protein expression. We found that 19 (76.0%) proximal-type Epithelioid Sarcoma and 27 (93.1%) distal-type Epithelioid Sarcoma showed loss of SMARCB1/INI1 protein expression. Analysis of 39 cases with loss of protein expression revealed 4 cases (10.3%) with SMARCB1/INI1 gene alterations at the DNA level (homozygous deletion, 2; 1- or 2-bp deletion, 2) that could have induced the loss of gene products, and all 4 of these were proximal-type Epithelioid Sarcoma. Epithelioid Sarcoma was thus associated with a high frequency of loss of SMARCB1/INI1 protein expression similar to that in malignant rhabdoid tumor. However, the frequency of SMARCB1/INI1 gene alteration at the DNA level in proximal-type Epithelioid Sarcoma was significantly lower than that in malignant rhabdoid tumor. In addition, the prognosis of patients with malignant rhabdoid tumor is significantly worse than that of patients with proximal-type Epithelioid Sarcoma (P = .001). Therefore, proximal-type Epithelioid Sarcoma and malignant rhabdoid tumor are suggested to be distinctive tumors with respect to the mechanism of the loss of SMARCB1/INI1 protein expression. Analysis of alterations in the SMARCB1/INI1 gene may thus be a useful diagnostic tool to distinguish proximal-type Epithelioid Sarcoma from malignant rhabdoid tumor.
Kenichi Kohashi - One of the best experts on this subject based on the ideXlab platform.
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swi snf chromatin remodeling complex status in smarcb1 ini1 preserved Epithelioid Sarcoma
The American Journal of Surgical Pathology, 2018Co-Authors: Kenichi Kohashi, Hidetaka Yamamoto, Tomoaki Taguchi, Yukihide Iwamoto, Yuichi Yamada, Izumi Kinoshita, Yoshinao OdaAbstract:The SWI/SNF chromatin-remodeling complex, which is composed of evolutionarily conserved core subunits such as SMARCB1/INI1 (INI1), SMARCA4/BRG1 (BRG1), SMARCC1/BAF155 (BAF155), and SMARCC2/BAF170 (BAF170), can be viewed as the prototype of an epigenetic regulator of gene expression that is involved in tumor suppression. Epithelioid Sarcoma, which classified as a tumor of uncertain differentiation, shows an almost complete loss of INI1. However, some cases of Epithelioid Sarcoma have preserved INI1, and the clinicopathologic features of these cases are uncertain. To date, there has been no investigation focused on the SWI/SNF chromatin-remodeling complex in INI1-preserved Epithelioid Sarcoma cases. First, an investigation of INI1 immunoexpression statuses in 60 formalin-fixed paraffin-embedded Epithelioid Sarcoma specimens (proximal type, 29 cases; conventional type, 31 cases) was performed. In the available INI1-preserved Epithelioid Sarcoma cases, we analyzed the BRG1, BAF155, and BAF170 protein expressions. INI1 preservation was observed in 6 of 29 (21%) proximal-type and 2 of 31 (6%) conventional-type Epithelioid Sarcoma cases. Six cases of INI1-preserved Epithelioid Sarcomas of proximal type were available for further immunohistochemical study. One proximal type showed loss of BAF170, and 2 proximal-type cases revealed loss of BRG1 with preservation of the other remaining core subunit proteins. One proximal-type case showed a mosaic pattern of BRG1 and loss of BAF155. However, in the remaining 2 proximal-type cases, all core subunit proteins were preserved. Overall, these results suggest that loss of expression of SWI/SNF chromatin-remodeling complex proteins has an important role in tumorigenesis. The remaining 2 INI1-preserved Epithelioid Sarcoma cases may have had other abnormalities causing dysfunction of SWI/SNF chromatin remodeling.
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infrequent smarcb1 ini1 gene alteration in Epithelioid Sarcoma a useful tool in distinguishing Epithelioid Sarcoma from malignant rhabdoid tumor
Human Pathology, 2009Co-Authors: Kenichi Kohashi, Teiyu Izumi, Yoshinao Oda, Hidetaka Yamamoto, Sadafumi Tamiya, Tomoaki Taguchi, Yukihide Iwamoto, Tadashi Hasegawa, Masazumi TsuneyoshiAbstract:Loss of SMARCB1/INI1 protein expression is considered useful for confirming a histologic diagnosis of malignant rhabdoid tumor. However, loss of SMARCB1/INI1 protein expression has recently been reported in other tumors as well, including a few cases of Epithelioid Sarcoma. In addition, the histopathologic differences between proximal-type Epithelioid Sarcoma and malignant rhabdoid tumor have not been conclusively defined. We analyzed SMARCB1/INI1 protein expression in 54 Epithelioid Sarcoma (proximal-type, 25; distal-type, 29) and examined alterations of the SMARCB1/INI1 gene in the cases lacking protein expression. We found that 19 (76.0%) proximal-type Epithelioid Sarcoma and 27 (93.1%) distal-type Epithelioid Sarcoma showed loss of SMARCB1/INI1 protein expression. Analysis of 39 cases with loss of protein expression revealed 4 cases (10.3%) with SMARCB1/INI1 gene alterations at the DNA level (homozygous deletion, 2; 1- or 2-bp deletion, 2) that could have induced the loss of gene products, and all 4 of these were proximal-type Epithelioid Sarcoma. Epithelioid Sarcoma was thus associated with a high frequency of loss of SMARCB1/INI1 protein expression similar to that in malignant rhabdoid tumor. However, the frequency of SMARCB1/INI1 gene alteration at the DNA level in proximal-type Epithelioid Sarcoma was significantly lower than that in malignant rhabdoid tumor. In addition, the prognosis of patients with malignant rhabdoid tumor is significantly worse than that of patients with proximal-type Epithelioid Sarcoma (P = .001). Therefore, proximal-type Epithelioid Sarcoma and malignant rhabdoid tumor are suggested to be distinctive tumors with respect to the mechanism of the loss of SMARCB1/INI1 protein expression. Analysis of alterations in the SMARCB1/INI1 gene may thus be a useful diagnostic tool to distinguish proximal-type Epithelioid Sarcoma from malignant rhabdoid tumor.
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Infrequent SMARCB1/INI1 gene alteration in Epithelioid Sarcoma: a useful tool in distinguishing Epithelioid Sarcoma from malignant rhabdoid tumor ☆
Human pathology, 2008Co-Authors: Kenichi Kohashi, Teiyu Izumi, Yoshinao Oda, Hidetaka Yamamoto, Sadafumi Tamiya, Tomoaki Taguchi, Yukihide Iwamoto, Tadashi Hasegawa, Masazumi TsuneyoshiAbstract:Loss of SMARCB1/INI1 protein expression is considered useful for confirming a histologic diagnosis of malignant rhabdoid tumor. However, loss of SMARCB1/INI1 protein expression has recently been reported in other tumors as well, including a few cases of Epithelioid Sarcoma. In addition, the histopathologic differences between proximal-type Epithelioid Sarcoma and malignant rhabdoid tumor have not been conclusively defined. We analyzed SMARCB1/INI1 protein expression in 54 Epithelioid Sarcoma (proximal-type, 25; distal-type, 29) and examined alterations of the SMARCB1/INI1 gene in the cases lacking protein expression. We found that 19 (76.0%) proximal-type Epithelioid Sarcoma and 27 (93.1%) distal-type Epithelioid Sarcoma showed loss of SMARCB1/INI1 protein expression. Analysis of 39 cases with loss of protein expression revealed 4 cases (10.3%) with SMARCB1/INI1 gene alterations at the DNA level (homozygous deletion, 2; 1- or 2-bp deletion, 2) that could have induced the loss of gene products, and all 4 of these were proximal-type Epithelioid Sarcoma. Epithelioid Sarcoma was thus associated with a high frequency of loss of SMARCB1/INI1 protein expression similar to that in malignant rhabdoid tumor. However, the frequency of SMARCB1/INI1 gene alteration at the DNA level in proximal-type Epithelioid Sarcoma was significantly lower than that in malignant rhabdoid tumor. In addition, the prognosis of patients with malignant rhabdoid tumor is significantly worse than that of patients with proximal-type Epithelioid Sarcoma (P = .001). Therefore, proximal-type Epithelioid Sarcoma and malignant rhabdoid tumor are suggested to be distinctive tumors with respect to the mechanism of the loss of SMARCB1/INI1 protein expression. Analysis of alterations in the SMARCB1/INI1 gene may thus be a useful diagnostic tool to distinguish proximal-type Epithelioid Sarcoma from malignant rhabdoid tumor.
Yoshinao Oda - One of the best experts on this subject based on the ideXlab platform.
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swi snf chromatin remodeling complex status in smarcb1 ini1 preserved Epithelioid Sarcoma
The American Journal of Surgical Pathology, 2018Co-Authors: Kenichi Kohashi, Hidetaka Yamamoto, Tomoaki Taguchi, Yukihide Iwamoto, Yuichi Yamada, Izumi Kinoshita, Yoshinao OdaAbstract:The SWI/SNF chromatin-remodeling complex, which is composed of evolutionarily conserved core subunits such as SMARCB1/INI1 (INI1), SMARCA4/BRG1 (BRG1), SMARCC1/BAF155 (BAF155), and SMARCC2/BAF170 (BAF170), can be viewed as the prototype of an epigenetic regulator of gene expression that is involved in tumor suppression. Epithelioid Sarcoma, which classified as a tumor of uncertain differentiation, shows an almost complete loss of INI1. However, some cases of Epithelioid Sarcoma have preserved INI1, and the clinicopathologic features of these cases are uncertain. To date, there has been no investigation focused on the SWI/SNF chromatin-remodeling complex in INI1-preserved Epithelioid Sarcoma cases. First, an investigation of INI1 immunoexpression statuses in 60 formalin-fixed paraffin-embedded Epithelioid Sarcoma specimens (proximal type, 29 cases; conventional type, 31 cases) was performed. In the available INI1-preserved Epithelioid Sarcoma cases, we analyzed the BRG1, BAF155, and BAF170 protein expressions. INI1 preservation was observed in 6 of 29 (21%) proximal-type and 2 of 31 (6%) conventional-type Epithelioid Sarcoma cases. Six cases of INI1-preserved Epithelioid Sarcomas of proximal type were available for further immunohistochemical study. One proximal type showed loss of BAF170, and 2 proximal-type cases revealed loss of BRG1 with preservation of the other remaining core subunit proteins. One proximal-type case showed a mosaic pattern of BRG1 and loss of BAF155. However, in the remaining 2 proximal-type cases, all core subunit proteins were preserved. Overall, these results suggest that loss of expression of SWI/SNF chromatin-remodeling complex proteins has an important role in tumorigenesis. The remaining 2 INI1-preserved Epithelioid Sarcoma cases may have had other abnormalities causing dysfunction of SWI/SNF chromatin remodeling.
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infrequent smarcb1 ini1 gene alteration in Epithelioid Sarcoma a useful tool in distinguishing Epithelioid Sarcoma from malignant rhabdoid tumor
Human Pathology, 2009Co-Authors: Kenichi Kohashi, Teiyu Izumi, Yoshinao Oda, Hidetaka Yamamoto, Sadafumi Tamiya, Tomoaki Taguchi, Yukihide Iwamoto, Tadashi Hasegawa, Masazumi TsuneyoshiAbstract:Loss of SMARCB1/INI1 protein expression is considered useful for confirming a histologic diagnosis of malignant rhabdoid tumor. However, loss of SMARCB1/INI1 protein expression has recently been reported in other tumors as well, including a few cases of Epithelioid Sarcoma. In addition, the histopathologic differences between proximal-type Epithelioid Sarcoma and malignant rhabdoid tumor have not been conclusively defined. We analyzed SMARCB1/INI1 protein expression in 54 Epithelioid Sarcoma (proximal-type, 25; distal-type, 29) and examined alterations of the SMARCB1/INI1 gene in the cases lacking protein expression. We found that 19 (76.0%) proximal-type Epithelioid Sarcoma and 27 (93.1%) distal-type Epithelioid Sarcoma showed loss of SMARCB1/INI1 protein expression. Analysis of 39 cases with loss of protein expression revealed 4 cases (10.3%) with SMARCB1/INI1 gene alterations at the DNA level (homozygous deletion, 2; 1- or 2-bp deletion, 2) that could have induced the loss of gene products, and all 4 of these were proximal-type Epithelioid Sarcoma. Epithelioid Sarcoma was thus associated with a high frequency of loss of SMARCB1/INI1 protein expression similar to that in malignant rhabdoid tumor. However, the frequency of SMARCB1/INI1 gene alteration at the DNA level in proximal-type Epithelioid Sarcoma was significantly lower than that in malignant rhabdoid tumor. In addition, the prognosis of patients with malignant rhabdoid tumor is significantly worse than that of patients with proximal-type Epithelioid Sarcoma (P = .001). Therefore, proximal-type Epithelioid Sarcoma and malignant rhabdoid tumor are suggested to be distinctive tumors with respect to the mechanism of the loss of SMARCB1/INI1 protein expression. Analysis of alterations in the SMARCB1/INI1 gene may thus be a useful diagnostic tool to distinguish proximal-type Epithelioid Sarcoma from malignant rhabdoid tumor.
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Infrequent SMARCB1/INI1 gene alteration in Epithelioid Sarcoma: a useful tool in distinguishing Epithelioid Sarcoma from malignant rhabdoid tumor ☆
Human pathology, 2008Co-Authors: Kenichi Kohashi, Teiyu Izumi, Yoshinao Oda, Hidetaka Yamamoto, Sadafumi Tamiya, Tomoaki Taguchi, Yukihide Iwamoto, Tadashi Hasegawa, Masazumi TsuneyoshiAbstract:Loss of SMARCB1/INI1 protein expression is considered useful for confirming a histologic diagnosis of malignant rhabdoid tumor. However, loss of SMARCB1/INI1 protein expression has recently been reported in other tumors as well, including a few cases of Epithelioid Sarcoma. In addition, the histopathologic differences between proximal-type Epithelioid Sarcoma and malignant rhabdoid tumor have not been conclusively defined. We analyzed SMARCB1/INI1 protein expression in 54 Epithelioid Sarcoma (proximal-type, 25; distal-type, 29) and examined alterations of the SMARCB1/INI1 gene in the cases lacking protein expression. We found that 19 (76.0%) proximal-type Epithelioid Sarcoma and 27 (93.1%) distal-type Epithelioid Sarcoma showed loss of SMARCB1/INI1 protein expression. Analysis of 39 cases with loss of protein expression revealed 4 cases (10.3%) with SMARCB1/INI1 gene alterations at the DNA level (homozygous deletion, 2; 1- or 2-bp deletion, 2) that could have induced the loss of gene products, and all 4 of these were proximal-type Epithelioid Sarcoma. Epithelioid Sarcoma was thus associated with a high frequency of loss of SMARCB1/INI1 protein expression similar to that in malignant rhabdoid tumor. However, the frequency of SMARCB1/INI1 gene alteration at the DNA level in proximal-type Epithelioid Sarcoma was significantly lower than that in malignant rhabdoid tumor. In addition, the prognosis of patients with malignant rhabdoid tumor is significantly worse than that of patients with proximal-type Epithelioid Sarcoma (P = .001). Therefore, proximal-type Epithelioid Sarcoma and malignant rhabdoid tumor are suggested to be distinctive tumors with respect to the mechanism of the loss of SMARCB1/INI1 protein expression. Analysis of alterations in the SMARCB1/INI1 gene may thus be a useful diagnostic tool to distinguish proximal-type Epithelioid Sarcoma from malignant rhabdoid tumor.
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Prognostic significance of dysadherin expression in Epithelioid Sarcoma and its diagnostic utility in distinguishing Epithelioid Sarcoma from malignant rhabdoid tumor
Modern pathology : an official journal of the United States and Canadian Academy of Pathology Inc, 2006Co-Authors: Teiyu Izumi, Yoshinao Oda, Tadashi Hasegawa, Yukihiro Nakanishi, Hiroshi Iwasaki, Hiroshi Sonobe, Hiroaki Goto, Hidenari Kusakabe, Tomonari Takahira, Chikashi KobayashiAbstract: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.
Tadashi Hasegawa - One of the best experts on this subject based on the ideXlab platform.
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infrequent smarcb1 ini1 gene alteration in Epithelioid Sarcoma a useful tool in distinguishing Epithelioid Sarcoma from malignant rhabdoid tumor
Human Pathology, 2009Co-Authors: Kenichi Kohashi, Teiyu Izumi, Yoshinao Oda, Hidetaka Yamamoto, Sadafumi Tamiya, Tomoaki Taguchi, Yukihide Iwamoto, Tadashi Hasegawa, Masazumi TsuneyoshiAbstract:Loss of SMARCB1/INI1 protein expression is considered useful for confirming a histologic diagnosis of malignant rhabdoid tumor. However, loss of SMARCB1/INI1 protein expression has recently been reported in other tumors as well, including a few cases of Epithelioid Sarcoma. In addition, the histopathologic differences between proximal-type Epithelioid Sarcoma and malignant rhabdoid tumor have not been conclusively defined. We analyzed SMARCB1/INI1 protein expression in 54 Epithelioid Sarcoma (proximal-type, 25; distal-type, 29) and examined alterations of the SMARCB1/INI1 gene in the cases lacking protein expression. We found that 19 (76.0%) proximal-type Epithelioid Sarcoma and 27 (93.1%) distal-type Epithelioid Sarcoma showed loss of SMARCB1/INI1 protein expression. Analysis of 39 cases with loss of protein expression revealed 4 cases (10.3%) with SMARCB1/INI1 gene alterations at the DNA level (homozygous deletion, 2; 1- or 2-bp deletion, 2) that could have induced the loss of gene products, and all 4 of these were proximal-type Epithelioid Sarcoma. Epithelioid Sarcoma was thus associated with a high frequency of loss of SMARCB1/INI1 protein expression similar to that in malignant rhabdoid tumor. However, the frequency of SMARCB1/INI1 gene alteration at the DNA level in proximal-type Epithelioid Sarcoma was significantly lower than that in malignant rhabdoid tumor. In addition, the prognosis of patients with malignant rhabdoid tumor is significantly worse than that of patients with proximal-type Epithelioid Sarcoma (P = .001). Therefore, proximal-type Epithelioid Sarcoma and malignant rhabdoid tumor are suggested to be distinctive tumors with respect to the mechanism of the loss of SMARCB1/INI1 protein expression. Analysis of alterations in the SMARCB1/INI1 gene may thus be a useful diagnostic tool to distinguish proximal-type Epithelioid Sarcoma from malignant rhabdoid tumor.
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Infrequent SMARCB1/INI1 gene alteration in Epithelioid Sarcoma: a useful tool in distinguishing Epithelioid Sarcoma from malignant rhabdoid tumor ☆
Human pathology, 2008Co-Authors: Kenichi Kohashi, Teiyu Izumi, Yoshinao Oda, Hidetaka Yamamoto, Sadafumi Tamiya, Tomoaki Taguchi, Yukihide Iwamoto, Tadashi Hasegawa, Masazumi TsuneyoshiAbstract:Loss of SMARCB1/INI1 protein expression is considered useful for confirming a histologic diagnosis of malignant rhabdoid tumor. However, loss of SMARCB1/INI1 protein expression has recently been reported in other tumors as well, including a few cases of Epithelioid Sarcoma. In addition, the histopathologic differences between proximal-type Epithelioid Sarcoma and malignant rhabdoid tumor have not been conclusively defined. We analyzed SMARCB1/INI1 protein expression in 54 Epithelioid Sarcoma (proximal-type, 25; distal-type, 29) and examined alterations of the SMARCB1/INI1 gene in the cases lacking protein expression. We found that 19 (76.0%) proximal-type Epithelioid Sarcoma and 27 (93.1%) distal-type Epithelioid Sarcoma showed loss of SMARCB1/INI1 protein expression. Analysis of 39 cases with loss of protein expression revealed 4 cases (10.3%) with SMARCB1/INI1 gene alterations at the DNA level (homozygous deletion, 2; 1- or 2-bp deletion, 2) that could have induced the loss of gene products, and all 4 of these were proximal-type Epithelioid Sarcoma. Epithelioid Sarcoma was thus associated with a high frequency of loss of SMARCB1/INI1 protein expression similar to that in malignant rhabdoid tumor. However, the frequency of SMARCB1/INI1 gene alteration at the DNA level in proximal-type Epithelioid Sarcoma was significantly lower than that in malignant rhabdoid tumor. In addition, the prognosis of patients with malignant rhabdoid tumor is significantly worse than that of patients with proximal-type Epithelioid Sarcoma (P = .001). Therefore, proximal-type Epithelioid Sarcoma and malignant rhabdoid tumor are suggested to be distinctive tumors with respect to the mechanism of the loss of SMARCB1/INI1 protein expression. Analysis of alterations in the SMARCB1/INI1 gene may thus be a useful diagnostic tool to distinguish proximal-type Epithelioid Sarcoma from malignant rhabdoid tumor.
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Prognostic significance of dysadherin expression in Epithelioid Sarcoma and its diagnostic utility in distinguishing Epithelioid Sarcoma from malignant rhabdoid tumor
Modern pathology : an official journal of the United States and Canadian Academy of Pathology Inc, 2006Co-Authors: Teiyu Izumi, Yoshinao Oda, Tadashi Hasegawa, Yukihiro Nakanishi, Hiroshi Iwasaki, Hiroshi Sonobe, Hiroaki Goto, Hidenari Kusakabe, Tomonari Takahira, Chikashi KobayashiAbstract: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.
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Undifferentiated carcinoma of the vulva mimicking Epithelioid Sarcoma.
The American journal of surgical pathology, 1991Co-Authors: Eiji Kudo, Tadashi Hasegawa, Takanori Hirose, Yoshiyuki Fujii, Hiroyasu Ino, Kazuo HizawaAbstract:We report an undifferentiated sweat gland carcinoma of the vulva in an 80-year-old woman. The tumor, which was located in the right labium majus, resembled an Epithelioid Sarcoma histologically; it had a granulomatous appearance with multiple tumor nodules containing Epithelioid tumor cells. The tumor also contained rhabdoid cells; a large cluster of them showed histological features indistinguishable from those of a malignant rhabdoid tumor. Immunohistochemically, the tumor cells reacted not only for epithelial markers such as cytokeratins, EMA, and CEA, which are known to be expressed by Epithelioid Sarcoma, but also for CA125 and with monoclonal antibodies recognizing sweat gland structures--namely, EKH5 and EKH6. For comparison, two Epithelioid Sarcomas and two extrarenal malignant rhabdoid tumors were also studied. Of these tumors, only one extrarenal rhabdoid tumor reacted with EKH5, and none reacted for CA125. Electron-microscopic examination of the present tumor showed the presence of discontinuous basal laminae and tonofibril-like structures as well as primitive cell junctions and interdigitating filopodia. From these findings, we conclude that the tumor was an undifferentiated sweat gland carcinoma mimicking an Epithelioid Sarcoma. Findings in this case support the idea of the diverse histogenesis of extrarenal malignant rhabdoid tumors and indicate that electron microscopy is important for differentiating Epithelioid Sarcoma from skin adnexal carcinoma.
Yukihide Iwamoto - One of the best experts on this subject based on the ideXlab platform.
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swi snf chromatin remodeling complex status in smarcb1 ini1 preserved Epithelioid Sarcoma
The American Journal of Surgical Pathology, 2018Co-Authors: Kenichi Kohashi, Hidetaka Yamamoto, Tomoaki Taguchi, Yukihide Iwamoto, Yuichi Yamada, Izumi Kinoshita, Yoshinao OdaAbstract:The SWI/SNF chromatin-remodeling complex, which is composed of evolutionarily conserved core subunits such as SMARCB1/INI1 (INI1), SMARCA4/BRG1 (BRG1), SMARCC1/BAF155 (BAF155), and SMARCC2/BAF170 (BAF170), can be viewed as the prototype of an epigenetic regulator of gene expression that is involved in tumor suppression. Epithelioid Sarcoma, which classified as a tumor of uncertain differentiation, shows an almost complete loss of INI1. However, some cases of Epithelioid Sarcoma have preserved INI1, and the clinicopathologic features of these cases are uncertain. To date, there has been no investigation focused on the SWI/SNF chromatin-remodeling complex in INI1-preserved Epithelioid Sarcoma cases. First, an investigation of INI1 immunoexpression statuses in 60 formalin-fixed paraffin-embedded Epithelioid Sarcoma specimens (proximal type, 29 cases; conventional type, 31 cases) was performed. In the available INI1-preserved Epithelioid Sarcoma cases, we analyzed the BRG1, BAF155, and BAF170 protein expressions. INI1 preservation was observed in 6 of 29 (21%) proximal-type and 2 of 31 (6%) conventional-type Epithelioid Sarcoma cases. Six cases of INI1-preserved Epithelioid Sarcomas of proximal type were available for further immunohistochemical study. One proximal type showed loss of BAF170, and 2 proximal-type cases revealed loss of BRG1 with preservation of the other remaining core subunit proteins. One proximal-type case showed a mosaic pattern of BRG1 and loss of BAF155. However, in the remaining 2 proximal-type cases, all core subunit proteins were preserved. Overall, these results suggest that loss of expression of SWI/SNF chromatin-remodeling complex proteins has an important role in tumorigenesis. The remaining 2 INI1-preserved Epithelioid Sarcoma cases may have had other abnormalities causing dysfunction of SWI/SNF chromatin remodeling.
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infrequent smarcb1 ini1 gene alteration in Epithelioid Sarcoma a useful tool in distinguishing Epithelioid Sarcoma from malignant rhabdoid tumor
Human Pathology, 2009Co-Authors: Kenichi Kohashi, Teiyu Izumi, Yoshinao Oda, Hidetaka Yamamoto, Sadafumi Tamiya, Tomoaki Taguchi, Yukihide Iwamoto, Tadashi Hasegawa, Masazumi TsuneyoshiAbstract:Loss of SMARCB1/INI1 protein expression is considered useful for confirming a histologic diagnosis of malignant rhabdoid tumor. However, loss of SMARCB1/INI1 protein expression has recently been reported in other tumors as well, including a few cases of Epithelioid Sarcoma. In addition, the histopathologic differences between proximal-type Epithelioid Sarcoma and malignant rhabdoid tumor have not been conclusively defined. We analyzed SMARCB1/INI1 protein expression in 54 Epithelioid Sarcoma (proximal-type, 25; distal-type, 29) and examined alterations of the SMARCB1/INI1 gene in the cases lacking protein expression. We found that 19 (76.0%) proximal-type Epithelioid Sarcoma and 27 (93.1%) distal-type Epithelioid Sarcoma showed loss of SMARCB1/INI1 protein expression. Analysis of 39 cases with loss of protein expression revealed 4 cases (10.3%) with SMARCB1/INI1 gene alterations at the DNA level (homozygous deletion, 2; 1- or 2-bp deletion, 2) that could have induced the loss of gene products, and all 4 of these were proximal-type Epithelioid Sarcoma. Epithelioid Sarcoma was thus associated with a high frequency of loss of SMARCB1/INI1 protein expression similar to that in malignant rhabdoid tumor. However, the frequency of SMARCB1/INI1 gene alteration at the DNA level in proximal-type Epithelioid Sarcoma was significantly lower than that in malignant rhabdoid tumor. In addition, the prognosis of patients with malignant rhabdoid tumor is significantly worse than that of patients with proximal-type Epithelioid Sarcoma (P = .001). Therefore, proximal-type Epithelioid Sarcoma and malignant rhabdoid tumor are suggested to be distinctive tumors with respect to the mechanism of the loss of SMARCB1/INI1 protein expression. Analysis of alterations in the SMARCB1/INI1 gene may thus be a useful diagnostic tool to distinguish proximal-type Epithelioid Sarcoma from malignant rhabdoid tumor.
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Infrequent SMARCB1/INI1 gene alteration in Epithelioid Sarcoma: a useful tool in distinguishing Epithelioid Sarcoma from malignant rhabdoid tumor ☆
Human pathology, 2008Co-Authors: Kenichi Kohashi, Teiyu Izumi, Yoshinao Oda, Hidetaka Yamamoto, Sadafumi Tamiya, Tomoaki Taguchi, Yukihide Iwamoto, Tadashi Hasegawa, Masazumi TsuneyoshiAbstract:Loss of SMARCB1/INI1 protein expression is considered useful for confirming a histologic diagnosis of malignant rhabdoid tumor. However, loss of SMARCB1/INI1 protein expression has recently been reported in other tumors as well, including a few cases of Epithelioid Sarcoma. In addition, the histopathologic differences between proximal-type Epithelioid Sarcoma and malignant rhabdoid tumor have not been conclusively defined. We analyzed SMARCB1/INI1 protein expression in 54 Epithelioid Sarcoma (proximal-type, 25; distal-type, 29) and examined alterations of the SMARCB1/INI1 gene in the cases lacking protein expression. We found that 19 (76.0%) proximal-type Epithelioid Sarcoma and 27 (93.1%) distal-type Epithelioid Sarcoma showed loss of SMARCB1/INI1 protein expression. Analysis of 39 cases with loss of protein expression revealed 4 cases (10.3%) with SMARCB1/INI1 gene alterations at the DNA level (homozygous deletion, 2; 1- or 2-bp deletion, 2) that could have induced the loss of gene products, and all 4 of these were proximal-type Epithelioid Sarcoma. Epithelioid Sarcoma was thus associated with a high frequency of loss of SMARCB1/INI1 protein expression similar to that in malignant rhabdoid tumor. However, the frequency of SMARCB1/INI1 gene alteration at the DNA level in proximal-type Epithelioid Sarcoma was significantly lower than that in malignant rhabdoid tumor. In addition, the prognosis of patients with malignant rhabdoid tumor is significantly worse than that of patients with proximal-type Epithelioid Sarcoma (P = .001). Therefore, proximal-type Epithelioid Sarcoma and malignant rhabdoid tumor are suggested to be distinctive tumors with respect to the mechanism of the loss of SMARCB1/INI1 protein expression. Analysis of alterations in the SMARCB1/INI1 gene may thus be a useful diagnostic tool to distinguish proximal-type Epithelioid Sarcoma from malignant rhabdoid tumor.