Excellent Prognosis in a Subset of Patients with Ewing Sarcoma Identified at Diagnosis by CD56 Using Flow Cytometry

Ash, Susan; Luria, Drorit; Cohen, Ian J.; Goshen, Y.; Toledano, Helen; Issakov, Josephine; Yaniv, Isaac; Avigad, Smadar

doi:10.1158/1078-0432.ccr-10-3069

Cited by 24 publications

(21 citation statements)

References 43 publications

(63 reference statements)

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“…(2, 8, 13) Of particular interest, Ash and colleagues retrospectively analyzed 46 archival frozen BM samples from newly diagnosed ES patients (of which 35 BM samples were from patients with localized disease) using a similar multi-parametric flow cytometry method. They observed no significant differences in outcome and clinical parameters according to the level of occult BM involvement.…”

Section: Discussionmentioning

confidence: 99%

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Impact of Two Measures of Micrometastatic Disease on Clinical Outcomes in Patients with Newly Diagnosed Ewing Sarcoma: A Report from the Children's Oncology Group

Edwards

Epling

et al. 2016

Clinical Cancer Research

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Purpose Flow cytometry and RT-PCR can detect occult Ewing sarcoma (ES) cells in the blood and bone marrow (BM). These techniques were used to evaluate the prognostic significance of micrometastatic disease in ES. Experimental Design Newly diagnosed patients with ES were enrolled on two prospective multi-center studies. In the flow cytometry cohort, patients were defined as “positive” for BM micrometastatic disease if their CD99+/CD45− values were above the upper limit in 22 control patients. In the PCR cohort, RT-PCR on blood or BM samples classified the patients as “positive” or “negative” for EWSR1/FLI1 translocations. The association between micrometastatic disease burden with clinical features and outcome was assessed. Co-expression of IGF-1R on detected tumor cells was performed in a subset of flow cytometry samples. Results The median total BM CD99+CD45− percent was 0.0012% (range 0–1.10%) in the flow cytometry cohort, with 14/109 (12.8%) of ES patients defined as “positive.” In the PCR cohort, 19.6% (44/225) patients were “positive” for any EWSR1/FLI1 translocation in blood or BM. There were no differences in baseline clinical features or event-free or overall survival between patients classified as “positive” vs. “negative” by either method. CD99+CD45− cells had significantly higher IGF-1R expression compared to CD45+ hematopoietic cells (mean geometric mean fluorescence intensity 982.7 vs. 190.9; p<0.001). Conclusion The detection of micrometastatic disease at initial diagnosis by flow cytometry or RT-PCR is not associated with outcome in newly diagnosed patients with ES. Flow cytometry provides a tool to characterize occult micrometastatic tumor cells for proteins of interest.

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Section: Discussionmentioning

confidence: 99%

“…(3, 6) Other PCR-based studies have not confirmed this finding(2, 8), nor did a small retrospective study that utilized flow cytometry to quantify BM micrometastatic disease burden. (13) Beyond initial diagnosis, the persistence of PB and/or BM fusion transcripts after chemotherapy has been shown to confer an adverse prognosis. (2)…”

Section: Introductionmentioning

confidence: 99%

Impact of Two Measures of Micrometastatic Disease on Clinical Outcomes in Patients with Newly Diagnosed Ewing Sarcoma: A Report from the Children's Oncology Group

Edwards

Epling

et al. 2016

Clinical Cancer Research

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“…Roughly half of the patients with localized disease at diagnosis will relapse within 5 years or later after completing the extensive multimodal therapy [3]. Based on the aggressive clinical course and relatively low curative rate, it has been proposed that ES may be a systemic disease characterized by micrometastases at submicroscopic level [4–7]. …”

Section: Introductionmentioning

confidence: 99%

Gene expression profiling of peripheral blood cells: new insights into Ewing sarcoma biology and clinical applications

et al. 2014

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Ewing sarcoma (ES) is a group of highly aggressive small round cell tumors of bone or soft tissue with high metastatic potential and low cure rate. ES tumors are associated with a rapid osteolysis and necrosis. The currently accepted clinical prognostic parameters do not accurately predict survival of high-risk patients. Moreover, neither the subtype of EWS–FLI1/ERG in the tumor, nor the detection of fusion transcripts in the peripheral blood (PB) samples, has prognostic value in ES patients. We evaluated the prevalence of circulating tumor cells (CTCs) in 34 adult ES patients. Since CTCs were confirmed in only small subset of patients, we further explored the expression profiles of PB leukocytes using a panel of genes associated with immune system status and increased tumor invasiveness. Moreover, we analyzed the alterations of the routine blood tests in the examined cohort of patients and correlated our findings with the clinical outcome. A uniform decrease in ZAP70 expression in PB cells among all ES patients, as compared to healthy individuals, was observed. Monocytosis and the abnormal expression of CDH2 and CDT2 genes in the PB cells significantly correlated with poor prognosis in ES patients. Our study supports the previously proposed hypothesis of systemic nature of ES. Based on the PB cell expression profiles, we propose a mechanism by which immune system may be involved in intensification of osteoclastogenesis and disease progression in ES patients. Moreover, we demonstrate the prognostic value of molecular PB testing at the time of routine histopathological diagnosis.

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“…In our tumor, the CD99 remained positive only in the undifferentiated cells and not in ganglion cells. If CD56 is frequently expressed in NB [3], it could be found in ES and was associated in good prognosis [10]. In our case, the positivity of CD56 was only found in NB-like foci of the tumor.…”

Section: Discussionmentioning

confidence: 50%

Extraosseous Ewing sarcoma with foci of neuroblastoma-like differentiation associated with EWSR1(Ewing sarcoma breakpoint region 1)/FLI1 translocation without prior chemotherapy

et al. 2012

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Excellent Prognosis in a Subset of Patients with Ewing Sarcoma Identified at Diagnosis by CD56 Using Flow Cytometry

Cited by 24 publications

References 43 publications

Impact of Two Measures of Micrometastatic Disease on Clinical Outcomes in Patients with Newly Diagnosed Ewing Sarcoma: A Report from the Children's Oncology Group

Impact of Two Measures of Micrometastatic Disease on Clinical Outcomes in Patients with Newly Diagnosed Ewing Sarcoma: A Report from the Children's Oncology Group

Gene expression profiling of peripheral blood cells: new insights into Ewing sarcoma biology and clinical applications

Extraosseous Ewing sarcoma with foci of neuroblastoma-like differentiation associated with EWSR1(Ewing sarcoma breakpoint region 1)/FLI1 translocation without prior chemotherapy

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