Prognostic significance of dysadherin expression in epithelioid sarcoma and its diagnostic utility in distinguishing epithelioid sarcoma from malignant rhabdoid tumor

Izumi, Toshihiro; Oda, Yoshinao; Hasegawa, Tadashi; Nakanishi, Yukihiro; Iwasaki, Hiroshi; Shinmoto, Hiroshi; Goto, Hiroaki; Kusakabe, Hidenari; Takahira, Tomonari; Kobayashi, Chikashi; Kawaguchi, Kohei; Saito, Tsuyoshi; Yamamoto, Hidetaka; Tamiya, Sadafumi; Iwamoto, Yukihide; Tsuneyoshi, Masazumi

doi:10.1038/modpathol.3800599

Cited by 45 publications

(39 citation statements)

References 32 publications

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“…(36) In ES, dysadherin expression was frequently observed in the proximal type, which has been reported as a more aggressive tumor compared with the distal type. (35) In synovial sarcoma, we also demonstrated that E-cadherin dysfunction caused by dysadherin expression is associated with E-cadherin repression and morphological change from the epithelioid to the spindle phenotype. (36) Concerning the diagnostic utility of adhesion molecules in STS, membranous expression of β-catenin (57) and dysadherin (35) is useful in distinguishing proximal-type ES from MRT.…”

Section: Multidrug Resistancementioning

confidence: 81%

“…(35) In synovial sarcoma, we also demonstrated that E-cadherin dysfunction caused by dysadherin expression is associated with E-cadherin repression and morphological change from the epithelioid to the spindle phenotype. (36) Concerning the diagnostic utility of adhesion molecules in STS, membranous expression of β-catenin (57) and dysadherin (35) is useful in distinguishing proximal-type ES from MRT. All the examined cases of proximal-type ES showed diffuse and strong membranous expression of β-catenin and dysadherin, whereas no cases of MRT had immunoreactivity for these proteins.…”

Section: Multidrug Resistancementioning

confidence: 81%

“…(73) Dysadherin is a cancer-associated cell membrane glycoprotein that downregulates the expression of E-cadherin and promotes metastasis. Dysadherin expression was found to be an independent poor prognostic factor in ES (35) and synovial sarcoma. (36) In ES, dysadherin expression was frequently observed in the proximal type, which has been reported as a more aggressive tumor compared with the distal type.…”

Section: Multidrug Resistancementioning

confidence: 99%

“…(56) MRT and proximal-type epithelioid sarcoma share the same morphological findings, and their differential diagnosis is often problematic. (35,57) Initially, some investigators demonstrated abnormalities in the long arm of chromosome 22 and deletion or mutation of the SMARCB1/INI1 gene in renal and extrarenal MRT. (58) The SMARCB1/INI1 gene is a member of the ATP-dependent SWI/SNF chromatin-remodeling complex, and has been suggested as a candidate specific tumor-suppressor gene in MRT.…”

Section: Smarcb1/ini1mentioning

confidence: 99%

“…Mixed STS RT-PCR High histological grade (31) YB-1 Synovial sarcoma IHC Poor prognosis, high proliferative rate (32) Embryonal RMS IHC High proliferative rate (33) Adhesion molecule E-Cadherin Synovial sarcoma IHC Poor prognosis (34) α-Catenin Synovial sarcoma IHC Poor prognosis (34) β-Catenin Synovial sarcoma IHC Poor prognosis, high proliferative rate (34) Dysadherin Epithelioid sarcoma IHC Poor prognosis, proximal type (35) Synovial sarcoma IHC Poor prognosis (36) doi: 10.1111/j.1349-7006.2008.01024.x © 2008 Japanese Cancer Association of p53 and MDM2 protein expression in the same tumor are of high prognostic relevance in mixed-type STS. (9) High MDM2 mRNA level has also been reported as a predictive adverse prognostic factor.…”

Section: Ss18-ssx1mentioning

confidence: 99%

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Recent advances in the molecular pathology of soft tissue sarcoma: Implications for diagnosis, patient prognosis, and molecular target therapy in the future

Oda

Tsuneyoshi

2009

Cancer Science

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In the present paper, recent advances in the molecular pathology of soft tissue sarcomas (STS) and the implications for their prognostic value are reviewed, and the potential targets of molecular therapy are discussed. According to the molecular genetic aspect, STS are divided into two groups: chromosome translocation-associated sarcomas and sarcomas without specific translocation. In the former group, specific fusion transcripts, such as SS18-SSX, EWS-FLI1, and PAX3-FKHR, could be detected in synovial sarcoma, Ewing's sarcoma and primitive neuroectodermal tumor, and alveolar rhabdomyosarcoma, respectively. The direct or indirect interactions between these fusion transcripts and cell cycle regulators have been elucidated by several investigators. Therefore, these fusion transcripts are promising candidates as molecular targets. As evaluated in carcinomas, alterations of several tumor-suppressor genes and adhesion molecules and overexpression of growth factors and their receptors have been extensively assessed in STS. In mixed-type STS, epidermal growth factor receptor overexpression was associated with decreased overall survival, suggesting the beneficial role of epidermal growth factor receptor inhibitors in STS. In malignant rhabdoid tumor and epithelioid sarcoma, frequent alteration of the SMARCB1/INI1 tumor-suppressor gene and the loss of its protein have been demonstrated, indicating that this molecule could be an effective target of these sarcomas. In sarcomas with epithelioid differentiation, such as synovial sarcoma and epithelioid sarcoma, overexpression of dysadherin, which downregulates E-cadherin expression, was a poor prognostic factor. In conclusion, further studies are necessary to search for effective and specific molecules for the inhibition of tumor growth in each type of STS, especially in sarcomas without specific translocation. (Cancer Sci 2009; 100: 200-208) S oft tissue sarcomas are relatively rare malignant neoplasms compared with carcinomas and other neoplasms, and they constitute less than 1% of all cancers. STS are composed of many histological subtypes, such as pleomorphic undifferentiated sarcoma or malignant fibrous histiocytoma, leiomayosarcoma, and liposarcoma. In addition to their wide variety of subtypes, it is often difficult to make an accurate histological diagnosis because certain kinds of STS share similar morphological features. However, it is important to make a definitive diagnosis so that adequate therapy can be administered in each case. Recently, several reciprocal chromosomal translocations and fusion transcripts have been proven to be characteristic of particular histological types (Table 1; Fig. 1). The detection of these fusion transcripts is useful for the differential diagnosis of histologically peculiar cases.In relapsed cases of STS complete remission is difficult, despite the conventional multidisciplinary therapy. Therefore, novel therapies such as molecular target therapy are required, especially in relapsed cases. Several investigators have analyzed tumor-...

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Section: Multidrug Resistancementioning

confidence: 81%

Section: Multidrug Resistancementioning

confidence: 81%

Section: Multidrug Resistancementioning

confidence: 99%

Section: Smarcb1/ini1mentioning

confidence: 99%

Section: Ss18-ssx1mentioning

confidence: 99%

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Recent advances in the molecular pathology of soft tissue sarcoma: Implications for diagnosis, patient prognosis, and molecular target therapy in the future

Oda

Tsuneyoshi

2009

Cancer Science

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SWI / SNF Chromatin Remodelling and Human Cancer

Reisman

Thompson

Marquez-Vilendrer

et al. 2016

Encyclopedia of Life Sciences

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Brahma (BRM) and Brahma‐related gene 1 (BRG1) are two mutually exclusively catalytic subunits of the switch in mating type/sucrose nonfermenting complex. These two key anticancer proteins are frequently targeted and silenced during cancer development. The anticancer function of BRM can be abrogated when it becomes acetylated or when it is epigenetically silenced. Central to BRM silencing is the presence of two inherited insertional polymorphisms within the BRM promoter that are statistically linked to cancer risk. Both BRM acetylation and silencing can be reversed by a number of compound families and might be important to how flavonoids and NSAIDS inhibit cancer. While BRG1 is very frequently mutated in most human cancers, it is more commonly inactivated by aberrant splicing and by an AKT‐pathway‐mediated‐translation block. While BRG1 and BRM are tied to deoxyribonucleic acid repair, growth control, differentiation, development, as well as epithelial–mesenchymal transition and are estimated to regulate 4–8% of the human genome, the inactivation of either protein is only modestly tumourigenic. This occurs in part because BRG1 and BRM are functionally redundant, which blunts the tumourigenic effect when only one gene is aberrantly silenced. Further insights into the mechanisms that regulate these genes may lead to novel therapeutic strategies that may reverse the silencing of these two important anticancer genes. Key Concepts Reversal of the epigenetic silencing of a gene may serve as a basis for drug therapy. Anticancer genes are epigenetically regulated by insertional polymorphisms. The functional redundancy of BRG1 and BRM thwarts cancer development. Post‐translational modification of BRM and BRG1 alters the cellular roles of these proteins from growth inhibitors to growth promoters. The loss of cofactors (i.e. BRG1 and/or BRM) for RB‐mediated‐growth inhibition could preclude the function of CDK inhibitors used clinically. Specific SWI/SNF subunits are commonly mutated and inactivated in specific cancer types. Diminished SWI/SNF activity, but not the complete abrogation of function, is tumourigenic.

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Update on SWI/SNF‐related gynecologic mesenchymal neoplasms: SMARCA4‐deficient uterine sarcoma and SMARCB1‐deficient vulvar neoplasms

Howitt

Folpe

2020

Genes Chromosomes & Cancer

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Our knowledge regarding the role of genes encoding the chromatin remodeling switch/sucrose non‐fermenting (SWI/SNF) complex in the initiation and progression of gynecologic malignancies continues to evolve. This review focuses on gynecologic tumors in which the sole or primary genetic alteration is in SMARCA4 or SMARCB1, two members of the SWI/SNF chromatin remodeling complex. In this review, we present a brief overview of the classical example of such tumors, ovarian small cell carcinoma of hypercalcemic type, and then a detailed review and update of SMARCB1‐deficient and SMARCA4‐deficient tumors of the uterus and vulva.

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Prognostic significance of dysadherin expression in epithelioid sarcoma and its diagnostic utility in distinguishing epithelioid sarcoma from malignant rhabdoid tumor

Cited by 45 publications

References 32 publications

Recent advances in the molecular pathology of soft tissue sarcoma: Implications for diagnosis, patient prognosis, and molecular target therapy in the future

Recent advances in the molecular pathology of soft tissue sarcoma: Implications for diagnosis, patient prognosis, and molecular target therapy in the future

SWI / SNF Chromatin Remodelling and Human Cancer

Update on SWI/SNF‐related gynecologic mesenchymal neoplasms: SMARCA4‐deficient uterine sarcoma and SMARCB1‐deficient vulvar neoplasms

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