<scp>PAX</scp>7 immunohistochemical evaluation of Ewing sarcoma and other small round cell tumours

Toki, Shunichi; Wakai, Susumu; Sekimizu, Masaya; Mori, Taisuke; Ichikawa, Hitoshi; Kawai, Akira; Yoshida, Akihiko

doi:10.1111/his.13689

Cited by 51 publications

(59 citation statements)

References 14 publications

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“…Hence, many groups have evaluated several potential diagnostic markers such as FLI1, NKX2-2, and PAX7 that could be used instead of the highly unspecific marker CD99 [40,57,58]. However, to the best of our knowledge, none of these proposed IHC markers completely fulfills the requirements of providing very high sensitivity and specificity for EwS at the same time.…”

Section: Discussionmentioning

confidence: 99%

“…However, to the best of our knowledge, none of these proposed IHC markers completely fulfills the requirements of providing very high sensitivity and specificity for EwS at the same time. While FLI1 is unable to confirm EwS cases with FET-non-FLI1 translocations [33,59], NKX2-2 and PAX7 lack specificity [60] and can be even strongly expressed in close morphological mimics such as EWSR1-NFATc2-positive sarcomas [40,57,58]. Besides, also Caveolin-1 [54,61], Cyclin-D1 [62], and NR0B1 [63] have been proposed as potential (auxiliary) IHC markers for EwS.…”

Section: Discussionmentioning

confidence: 99%

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High Specificity of BCL11B and GLG1 for EWSR1-FLI1 and EWSR1-ERG Positive Ewing Sarcoma

Orth¹,

Hölting²,

Dallmayer

et al. 2020

Cancers

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Ewing sarcoma (EwS) is an aggressive cancer displaying an undifferentiated small-round-cell histomorphology that can be easily confused with a broad spectrum of differential diagnoses. Using comparative transcriptomics and immunohistochemistry (IHC), we previously identified BCL11B and GLG1 as potential specific auxiliary IHC markers for EWSR1-FLI1-positive EwS. Herein, we aimed at validating the specificity of both markers in a far larger and independent cohort of EwS (including EWSR1-ERG-positive cases) and differential diagnoses. Furthermore, we evaluated their intra-tumoral expression heterogeneity. Thus, we stained tissue microarrays from 133 molecularly confirmed EwS cases and 320 samples from morphological mimics, as well as a series of patient-derived xenograft (PDX) models for BCL11B, GLG1, and CD99, and systematically assessed the immunoreactivity and optimal cut-offs for each marker. These analyses demonstrated that high BCL11B and/or GLG1 immunoreactivity in CD99-positive cases had a specificity of 97.5% and an accuracy of 87.4% for diagnosing EwS solely by IHC, and that the markers were expressed by EWSR1-ERG-positive EwS. Only little intra-tumoral heterogeneity in immunoreactivity was observed for differential diagnoses. These results indicate that BCL11B and GLG1 may help as specific auxiliary IHC markers in diagnosing EwS in conjunction with CD99, especially if confirmatory molecular diagnostics are not available.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

High Specificity of BCL11B and GLG1 for EWSR1-FLI1 and EWSR1-ERG Positive Ewing Sarcoma

Orth¹,

Hölting²,

Dallmayer

et al. 2020

Cancers

View full text Add to dashboard Cite

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“…Review of the published literature in the PubMed databank revealed 8 papers with at least minimal clinical information on 15 patients with tumors carrying the EWSR1-NFATC2 fusion [12, 13, 22, 26–30] (Table 1). Fourteen more cases lacking clinical information are mentioned in three further studies with a special focus on the molecular profiling of ES and ESLT [20, 23, 24]. Of the cases with clinical information, there was a striking male predominance with 14 males and 4 females.…”

Section: Review Of the Published Literaturementioning

confidence: 99%

“…Rare mesenchymal tumors carrying EWSR1-NFATC2 fusions have been assigned to ESLTs, probably due to partial CD99 expression and/or involvement of the EWSR1 [20–23]. However, recent studies demonstrate that not only histological features, but also the molecular profiles of such tumors differ from ESs [24–26].…”

Section: Introductionmentioning

confidence: 99%

EWSR1-NFATC2 and FUS-NFATC2 Gene Fusion-Associated Mesenchymal Tumors: Clinicopathologic Correlation and Literature Review

Bode-Lesniewska

Fritz

Exner

et al. 2019

Sarcoma

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The spectrum of mesenchymal tumors associated with rearrangements of the EWSR1 gene has been growing in recent years due to progress in molecular detection techniques. Originally identified as the gene involved in the pathogenesis of Ewing sarcoma, the EWSR1 gene is now known to be rearranged in diverse clinical and histopathological entities. The NFATC2 gene is one of the many translocation partners of EWSR1 in gene fusions in a morphologically typical, albeit rare, subgroup of mesenchymal tumors. Little is known about the clinical characteristics of tumors containing NFATC2 gene rearrangements since most of the few reports published describe molecular rather than clinical aspects. In the current study, we report three patients with tumors carrying the EWSR1-NFATC2 gene translocation, including one rare primary tumor of soft tissues. Another patient with a benign-appearing bone tumor with a unique FUS-NFATC2 gene translocation is described. In various mesenchymal tumors (e.g., myxoid/round cell liposarcoma, low-grade fibromyxoid sarcoma, or angiomatoid fibrous histiocytoma), the FUS gene, as a member of the TET family, may be alternatively rearranged instead of the EWSR1 gene without any noticeable influence on the microscopical appearance or clinical outcome. This fact seems not to apply to mesenchymal tumors with the involvement of the NFATC2 gene because both in our experience and according to the extensive literature review, they have different properties on the morphological and molecular level. Both ESWSR1-NFATC2 and FUS-NFATC2 fusion-carrying tumors do not show microscopical or clinical features of Ewing sarcoma.

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“…Another gene is GCKR, which play a significant role in cancer cell metabolism. The PAX7 gene play critical roles during fetal development and cancer growth [38]. Finally, IL2RA is an Interleukin 2 receptor subunit alpha protein involved in suppressing the activity of the immune system against tumor cells [39].…”

Section: Discussionmentioning

confidence: 99%

Epigenetic Alterations Associated with the Overall Survival and Recurrence Free Survival among Oral Squamous Cell Carcinoma Patients

Ghantous

Nashef

Abu-El-Naaj

2020

JCM

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Oral squamous cell carcinoma (OSCC) is a fatal disease caused by complex interactions between environmental, genomic, and epigenetic alterations. In the current study, we aimed to identify clusters of genes whose promoter methylation status correlated with various tested clinical features. Molecular datasets of genetic and methylation analysis based on whole-genome sequencing of 159 OSCC patients were obtained from the The Cancer Genome Atlas (TCGA) data portal. Genes were clustered based on their methylation status and were tested for their association with demographic, pathological, and clinical features of the patients. Overall, seven clusters of genes were revealed that showed a significant association with the overall survival/recurrence free survival of patients. The top ranked genes within cluster 4, which showed the worst prognosis, primarily acted as paraneoplastic genes, while the genes within cluster 6 primarily acted as anti-tumor genes. A significant difference was found regarding the mean age in the different clusters. No significant correlation was found between the tumor staging and the different clusters. In conclusion, our result provided a proof-of-principle for the existence of phenotypic diversity among the epigenetic clusters of OSCC and demonstrated the utility of the use epigenetics alterations in devolving new prognostic and therapeutics tools for OSCC patients.

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PAX7 immunohistochemical evaluation of Ewing sarcoma and other small round cell tumours

Cited by 51 publications

References 14 publications

High Specificity of BCL11B and GLG1 for EWSR1-FLI1 and EWSR1-ERG Positive Ewing Sarcoma

High Specificity of BCL11B and GLG1 for EWSR1-FLI1 and EWSR1-ERG Positive Ewing Sarcoma

EWSR1-NFATC2 and FUS-NFATC2 Gene Fusion-Associated Mesenchymal Tumors: Clinicopathologic Correlation and Literature Review

Epigenetic Alterations Associated with the Overall Survival and Recurrence Free Survival among Oral Squamous Cell Carcinoma Patients

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