7 research outputs found
Proliferation Index: A Continuous Model to Predict Prognosis in Patients with Tumours of the Ewing's Sarcoma Family
The prognostic value of proliferation index (PI) and apoptotic index (AI), caspase-8, -9 and -10 expression have been investigated in primary Ewing's sarcoma family of tumours (ESFT). Proliferating cells, detected by immunohistochemistry for Ki-67, were identified in 91% (91/100) of tumours with a median PI of 14 (range 0â87). Apoptotic cells, identified using the TUNEL assay, were detected in 96% (76/79) of ESFT; the median AI was 3 (range 0â33). Caspase-8 protein expression was negative (0) in 14% (11/79), low (1) in 33% (26/79), medium (2) in 38% (30/79) and high (3) in 15% (12/79) of tumours, caspase-9 expression was low (1) in 66% (39/59) and high (3) in 34% (20/59), and caspase-10 protein was low (1) in 37% (23/62) and negative (0) in 63% (39/62) of primary ESFT. There was no apparent relationship between caspase-8, -9 and -10 expression, PI and AI. PI was predictive of relapse-free survival (RFS; pâ=â0.011) and overall survival (OS; pâ=â<0.001) in a continuous model, whereas AI did not predict outcome. Patients with tumours expressing low levels of caspase-9 protein had a trend towards a worse RFS than patients with tumours expressing higher levels of caspase-9 protein (pâ=â0.054, log rank test), although expression of caspases-8, -9 and/or -10 did not significantly predict RFS or OS. In a multivariate analysis model that included tumour site, tumour volume, the presence of metastatic disease at diagnosis, PI and AI, PI independently predicts OS (pâ=â0.003). Consistent with previous publications, patients with pelvic tumours had a significantly worse OS than patients with tumours at other sites (pâ=â0.028); patients with a pelvic tumour and a PIâ„20 had a 6 fold-increased risk of death. These studies advocate the evaluation of PI in a risk model of outcome for patients with ESFT
The First European Interdisciplinary Ewing Sarcoma Research Summit
The European Network for Cancer Research in Children and Adolescents (ENCCA) provides an interaction platform for stakeholders in research and care of children with cancer. Among ENCCA objectives is the establishment of biology-based prioritization mechanisms for the selection of innovative targets, drugs, and prognostic markers for validation in clinical trials. Specifically for sarcomas, there is a burning need for novel treatment options, since current chemotherapeutic treatment protocols have met their limits. This is most obvious for metastatic Ewing sarcoma (ES), where long term survival rates are still below 20%. Despite significant progress in our understanding of ES biology, clinical translation of promising laboratory results has not yet taken place due to fragmentation of research and lack of an institutionalized discussion forum. To fill this gap, ENCCA assembled 30 European expert scientists and five North American opinion leaders in December 2011 to exchange thoughts and discuss the state of the art in ES research and latest results from the bench, and to propose biological studies and novel promising therapeutics for the upcoming European EWING2008 and EWING2012 clinical trials
A. Immunohistochemistry for Ki-67 performed on primary ESFT (5 ”m).
<p>Ki-67 protein was visualised with the DAB substrate, proliferating cells are identified by Ki-67 positive nuclei (see arrows). Immunohistochemistry performed in the absence of primary antibody was included to control for non-specific binding of the secondary antibody (No primary AB). Magnification Ă400. B. TUNEL on primary ESFT (5 ”m). Apoptotic cells were identified by TUNEL positive nuclei (see arrows). The TUNEL assay was performed in the absence TdT enzyme to control for non-specific staining (No enzyme). Magnification Ă400.</p
Immunohistochemistry on primary ESFT (5 ”m) for caspases-8, -9 and -10.
<p>Immunohistochemistry in the absence of primary antibody was to control for non-specific binding of the secondary antibody (No primary AB). Magnification of imagesâ=âĂ400. Caspase expression was scored as negative (0), low (1), medium (2) or high (3). A. Caspase-8 protein expression. B. Caspase-10 protein expression. C. Caspase-9 protein expression.</p
A. Kaplan Meier survival plots comparing the overall and relapse-free survival of patients with a tumour volume â„200 ml with that of patients with a tumour volume <200 ml, pâ=â0.019 and 0.0133 respectively; log rank test. Crosses indicate censored events.
<p>B. Kaplan Meier survival plots to compare the overall and relapse-free survival of patients with pelvic tumours to that of patients with tumours at other sites, pâ=â0.0185 and 0.0088 respectively; log rank test. Crosses indicate censored events.</p