Soft tissue sarcomas with complex genomic profiles

Guillou, Louis; Aurias, Alain

doi:10.1007/s00428-009-0853-4

Cited by 123 publications

(86 citation statements)

References 103 publications

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“…Our findings are comparable to the results reported previously on smaller IS cohorts (24,25). To the best of our knowledge, no other sarcoma reported thus far presents consistent PDGFRA amplification (35). Thus, given its specificity and high frequency of occurrence, the PDGFRA amplification in IS might be considered as a molecular hallmark of the entity.…”

Section: Discussionsupporting

confidence: 90%

Coactivated Platelet-Derived Growth Factor Receptor α and Epidermal Growth Factor Receptor Are Potential Therapeutic Targets in Intimal Sarcoma

et al. 2010

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Intimal sarcoma (IS) is a rare, malignant, and aggressive tumor that shows a relentless course with a concomitant low survival rate and for which no effective treatment is available. In this study, 21 cases of large arterial blood vessel IS were analyzed by immunohistochemistry and fluorescence in situ hybridization and selectively by karyotyping, array comparative genomic hybridization, sequencing, phospho-kinase antibody arrays, and Western immunoblotting in search for novel diagnostic markers and potential molecular therapeutic targets. Ex vivo immunoassays were applied to test the sensitivity of IS primary tumor cells to the receptor tyrosine kinase (RTK) inhibitors imatinib and dasatinib. We showed that amplification of platelet-derived growth factor receptor α (PDGFRA) is a common finding in IS, which should be considered as a molecular hallmark of this entity. This amplification is consistently associated with PDGFRA activation. Furthermore, the tumors reveal persistent activation of the epidermal growth factor receptor (EGFR), concurrent to PDGFRA activation. Activated PDGFRA and EGFR frequently coexist with amplification and overexpression of the MDM2 oncogene. Ex vivo immunoassays on primary IS cells from one case showed the potency of dasatinib to inhibit PDGFRA and downstream signaling pathways. Our findings provide a rationale for investigating therapies that target PDGFRA, EGFR, or MDM2 in IS. Given the clonal heterogeneity of this tumor type and the potential cross-talk between the PDGFRA and EGFR signaling pathways, targeting multiple RTKs and aberrant downstream effectors might be required to improve the therapeutic outcome for patients with this disease.

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Section: Discussionsupporting

confidence: 90%

Coactivated Platelet-Derived Growth Factor Receptor α and Epidermal Growth Factor Receptor Are Potential Therapeutic Targets in Intimal Sarcoma

et al. 2010

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“…As certain myxoid liposarcomas exhibit morphological similarities to round-cell liposarcomas and are similar in terms of histological progression, these two types are difficult to distinguish from each other. Additionally, in previous studies, mixed-type PRPLS was defined by the WHO as including two or more subtypes of liposarcoma (15,16). Thus, the present study allocated patients with myxoid and round cell PRPLS into one group, and patients with pleomorphic/mixed-type PRPLS into another group.…”

Section: Methodsmentioning

confidence: 99%

A retrospective, single‑center cohort study on 65ï¿½patients with primary retroperitoneal liposarcoma

Liu

et al. 2017

Oncol Lett

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Abstract. Primary retroperitoneal liposarcoma (PRPLS)is the most common soft tissue malignancy of the retroperitoneum. To determine the pathological features and the curative effects of surgery in patients with PRPLS, and to elucidate key prognostic factors, the present study retrospectively analyzed the clinical cases of 65 patients with PRPLS. Immunohistochemical analysis demonstrated that vimentin and Ki-67 are better indicators for PRPLS immunohistochemical diagnosis compared with S-100 protein. S-100 protein was predominantly expressed in well-differentiated PRPLS. Positive expression of vimentin and Ki-67 were observed in almost all PRPLS samples, and Ki-67 exhibited a higher expression level in high-grade PRPLS. The level of Ki-67 expression was negatively correlated with disease-specific survival (DSS). Survival analysis revealed that the pathological subtype and histological grade were associated with DSS and local recurrence in the patients, whereas the tumor burden was associated with DSS but not local recurrence. In addition, complete tumor resection and contiguous organ resection were able to improve DSS. Microscopically positive margins did not affect DSS, whereas gross margins did. Multivariate analysis revealed that pathological subtype, histological grade and contiguous organ resection were independent prognostic factors, and that histological grade was an independent factor for local recurrence. Patient sex and age at presentation were not independent factors associated with prognosis or local recurrence. Correlation analysis demonstrated that postoperative local recurrence significantly affected DSS, and local recurrence was the most common cause of mortality among patients. Histological grade was strongly associated with the invasion of adjacent organs but not with tumor burden. Furthermore, the tumor burden was not associated with recurrence or tumor invasion of adjacent organs. Ki-67 expression was associated with prognosis. Pathological subtype, histological grade and contiguous organ resection were independent prognostic factors, while histological grade was an independent factor which affected tumor recurrence.

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“…1 Molecular approaches have described three main genetics in these soft-tissue sarcomas: first, reciprocal translocations like in synovial sarcomas, second, specific mutations as observed in rhabdoid tumors, and finally, complex genomic profiles. [1][2][3] This last category is composed of tumors with high-level amplifications of chromosome 12 encompassing MDM2 and CDK4 loci (eg, well-differentiated and undifferentiated liposarcomas) (20% of cases) [3][4][5] and of tumors with very complex genomic imbalances (80% of cases), including mainly leiomyosarcomas and undifferentiated pleomorphic sarcomas. 4,5 Leiomyosarcomas correspond to 10-15% of softtissue sarcomas and display a strong smooth muscle differentiation.…”

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confidence: 99%

Smooth muscle differentiation identifies two classes of poorly differentiated pleomorphic sarcomas with distinct outcome

et al. 2014

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The clinical relevance of accurately diagnosing pleomorphic sarcomas has been shown, especially in cases of undifferentiated pleomorphic sarcomas with myogenic differentiation, which appear significantly more aggressive. To establish a new smooth muscle differentiation classification and to test its prognostic value, 412 sarcomas with complex genetics were examined by immunohistochemistry using four smooth muscle markers (calponin, h-caldesmon, transgelin and smooth muscle actin). Two tumor categories were first defined: tumors with positivity for all four markers and tumors with no or incomplete phenotypes. Multivariate analysis demonstrated that this classification method exhibited the strongest prognostic value compared with other prognostic factors, including histological classification. Secondly, incomplete or absent smooth muscle phenotype tumor group was then divided into subgroups by summing for each tumor the labeling intensities of all four markers for each tumors. A subgroup of tumors with an incomplete but strong smooth muscle differentiation phenotype presenting an intermediate metastatic risk was thus identified. Collectively, our results show that the smooth muscle differentiation classification method may be a useful diagnostic tool as well as a relevant prognostic tool for undifferentiated pleomorphic sarcomas.

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Soft tissue sarcomas with complex genomic profiles

Cited by 123 publications

References 103 publications

Coactivated Platelet-Derived Growth Factor Receptor α and Epidermal Growth Factor Receptor Are Potential Therapeutic Targets in Intimal Sarcoma

Coactivated Platelet-Derived Growth Factor Receptor α and Epidermal Growth Factor Receptor Are Potential Therapeutic Targets in Intimal Sarcoma

A retrospective, single‑center cohort study on 65ï¿½patients with primary retroperitoneal liposarcoma

Smooth muscle differentiation identifies two classes of poorly differentiated pleomorphic sarcomas with distinct outcome

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