Incidence and prognostic value of tumour cells detected by RT–PCR in peripheral blood stem cell collections from patients with Ewing tumour

Vermeulen, Jessica; Ballet, Steven; Oberlin, Odile; Peter, Martine; Pierron, Gaëlle; Longavenne, E.; Laurence, Valérie; Kanold, Justyna; Chastagner, Pascal; Lejars, Odile; Blay, Jean‐Yves; Marec‐Bérard, Perrine; Michon, Jean; Delattre, Olivier; Schleiermacher, Gudrun

doi:10.1038/sj.bjc.6603438

Cited by 24 publications

(11 citation statements)

References 31 publications

(50 reference statements)

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“…These chimeric transcripts have been detected by reverse-transcriptase PCR (RT-PCR) for the diagnosis of ES. Due to the high sensitivity of the RT-PCR assay, it can also be used for detecting circulating tumor cells in peripheral blood (PBL) and bone marrow (BM) samples (4)(5)(6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

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

Ash

Luria

Cohen

et al. 2011

Clinical Cancer Research

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Purpose: Ewing sarcoma (ES) is considered a systemic disease with the majority of patients harboring micrometastases at diagnosis. Multiparameter flow cytometry (MPFC) was used to detect ES cells in bone marrow (BM) of ES patients at diagnosis and to evaluate the prognostic significance of CD56 expression in BM samples.Experimental Design: BM samples from 46 ES patients, 6 tumor aspirates, 2 ES cell lines, and 10 control BM samples were analyzed by MPFC. ES cells were identified by the combination of CD45À/CD90þ/ CD99þ. CD56 was evaluated on these cells by a cutoff of 22%.Results: BM samples obtained from all patients at diagnosis were found to be positive for micrometastatic tumor cells assessed by CD99þ/CD90þ/CD45À expression. A total of 60% of the BM samples harbored high CD56 expression. There was a highly significant correlation between CD56 expression and progression-free survival (PFS; 69% in low/negative expression versus 30% in high expression groups, P ¼ 0.024). In patients with localized nonpelvic disease, those expressing low/negative CD56 had 100% PFS versus 40% in the high expressing group (P ¼ 0.02).

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Section: Introductionmentioning

confidence: 99%

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

Ash

Luria

Cohen

et al. 2011

Clinical Cancer Research

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“…Retrospective analyses also indicated that RT-PCR positivity was associated with a greater risk for recurrence as well as distant metastasis (7,8). In studies where stem cell harvests were tested, a high percentage showed positivity by nested RT-PCR (9), although tumor cell contamination did not influence event-free or overall survival among high-risk EFT patients (10).…”

mentioning

confidence: 99%

Novel Markers of Subclinical Disease for Ewing Family Tumors from Gene Expression Profiling

Cheung¹,

Feng²,

Danis³

et al. 2007

Clinical Cancer Research

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Purpose: Targeting subclinical disease in the bone marrow is particularly relevant in metastatic Ewing family tumors (EFT) where cure is difficult. Genome-wide expression arrays can uncover novel genes differentially expressed in tumors over normal marrow/blood, which may have potentials as markers of subclinical disease. Experimental Design: Gene expression array data were obtained on 28 EFT tumors using the Affymetrix U133 gene chip and compared with 10 normal blood samples. Ten genes with high tumor to blood ratios were identified. Quantitative reverse transcription-PCR was done to study (a) the dynamic range of detection of rare tumor cells, (b) the gene expression in normal blood/ marrow samples, (c) the gene expression among EFT tumors, and (d) the detection and prognostic impact of marker positivity in histology-negative diagnostic marrows of EFT patients. Before the era of effective chemotherapy, 5-year overall survival for Ewing family tumors (EFT) was V20%, largely because of uncontrolled subclinical metastatic disease (1). Despite the advent of modern chemoradiotherapy, the 5-year progression-free survival was only 30% among patients with overt metastases at the time of diagnosis, although many of them had achieved near complete clinical remission following induction therapy. In fact, even for patients presenting with localized disease at diagnosis, their overall survival decreased from 70% at 5 years to f50% at 10 years (1). The failure to cure is likely due to occult cancer cells that metastasize by hematogenous spread (2). Accurate and sensitive markers of EFT in the marrow or blood may help in the early detection of distant metastasis. More importantly, testing marrow or blood can facilitate the application of novel treatment approaches directed at minimal residual disease in the adjuvant setting, when there is no radiographic or histologic evidence of disease.All EFT tumors are characterized by similar chromosomal translocations that result in the fusion of the EWS gene on chromosome 22q12 with different ETS-related genes. More than 85% of analyzed cases of EFT are characterized by a t(11;22)(q24;q12) translocation. The most common fusion is made up of exon 7 of the EWS gene and exon 6 of the FLI1 gene (type 1 fusion), which was associated with favorable prognosis (3). Less common translocations (<10%) in EFT involve other members of the ETS family of transcription factors. These include ERG (located on chromosome 21), ETV1 (located on chromosome 7), E1AF (located on chromosome 17), and FEV (located on chromosome 2), resulting in t(21;22), t(7;22), t(17;22), and t(2;22) translocations, respectively (1). Among the chimeric transcripts resulting from such fusion, EWS-FLI1 (type 1 or 2) and EWS-ERG fusion transcripts are most widely used as molecular markers. Nested reverse transcription-PCR (RT-PCR) of fusion sequences (4) has enabled tumor detection at frequency of 10 -6 and has provided highly specific and sensitive tools for detecting circulating EFT in the bone marrow and blood. In fac...

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“…However, only 11 publications of 147 (7.5%) emerged from paediatric cancer research, mostly on sarcomas [34][35][36][37][38][39][40][41][42][43][44].…”

Section: V) Connective Tissue Cancer Network (Conticanet) [33]mentioning

confidence: 99%

More and better cure for an orphan: priorities for future paediatric cancer research in Europe – Meeting report of the EC-funded science-communication project DIRECT “Overcoming Cancer with Research”

Tallen

Dworzak

Gadner

et al. 2009

memo

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Background: Although cure rates for childhood cancer have improved from below 20% to more than 75% during the last 40 years, childhood cancer is still the number one killer amongst paediatric diseases. European paediatric cancer research also faces new challenges by the increasing number of childhood cancer survivors, some of whom experience signifi cantly altered life-quality due to serious psychosocial and medical long-term side-eff ects of the intensive cancer treatment. Hence, to achieve even higher quantity and quality of cure for Europe's children and adolescents with cancer, development of new treatment options is now required, as are intensifi ed epidemiological investigations into health and psycho-social issues of paediatric cancer survivors on the EU-level.Methods: Based on presentations and discussions at a recent meeting of leading European paediatric oncologists supported by the EC-funded science-communication project "DIRECT", this article discusses the situation of European paediatric cancer research under the EU-Framework Programmes (FPs).Results: Single, partially interlinking paediatric oncological research projects received EU-funding during the last three FPs. However, given the increased budgets for health research under the FP6 and FP7 together with their goal to improve the European Research Area (ERA), relatively few of the current challenges in European paediatric oncology have been covered so far when compared to the spending for adult cancer.Conclusion: Although still fragmented, current ECfunded projects in paediatric oncology would be amenable to a higher level of integration. In order to achieve a closer approach to "total cure" including all medical, psychological and social aspects, paediatric cancer should become a horizontal priority of European research funding.

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Incidence and prognostic value of tumour cells detected by RT–PCR in peripheral blood stem cell collections from patients with Ewing tumour

Cited by 24 publications

References 31 publications

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

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

Novel Markers of Subclinical Disease for Ewing Family Tumors from Gene Expression Profiling

More and better cure for an orphan: priorities for future paediatric cancer research in Europe – Meeting report of the EC-funded science-communication project DIRECT “Overcoming Cancer with Research”

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