44 research outputs found
Association of EWS-FLI1 Type 1 Fusion with Lower Proliferative Rate in Ewing’s Sarcoma
The Ewing's sarcoma (ES) family of tumors, including peripheral neuroectodermal
tumor (PNET), is defined genetically by specific chromosomal translocations
resulting in fusion of the EWS gene with a member of the ETS family of
transcription factors, either FLI1 (90-95%) or ERG (5-10%). A second level of
molecular genetic heterogeneity stems from the variation in the location of the
translocation breakpoints, resulting in the inclusion of different combinations
of exons from EWS and FLI1 (or ERG) in the fusion products. The most common type
of EWS-FLI1 fusion transcript, type 1, is associated with a favorable prognosis
and appears to encode a functionally weaker transactivator, compared to other
fusion types. We sought to determine whether the observed covariation of
structure, function, and clinical course correlates with tumor cell kinetic
parameters such as proliferative rate and apoptosis, and with expression of the
receptor for insulin-like growth factor I (IGF-1R). In a group of 86 ES/PNET with
defined EWS-ETS fusions (45 EWS-FLI1 type 1, 27 EWS-FLI1 non-type 1, 14 EWS-ERG),
we assessed proliferation rate by immunostaining for Ki-67 using MIB1 antibody (n
= 85), apoptosis by TUNEL assay (n = 66), and IGF-1R expression by immunostaining
with antibody 1H7 (n = 78). Ki-67 proliferative index was lower in tumors with
EWS-FLI1 type 1 than those with non-type 1 EWS-FLI1, whether analyzed as a
continuous (P = 0.049) or categorical (P = 0.047) variable. Logistic regression
analysis suggests that this association was secondary to the association of type
1 EWS-FLI1 and lower IGF-1R expression (P = 0.04). Comparing EWS-FLI1 to EWS-ERG
cases, Ki-67 proliferative index was higher in the latter (P = 0.01, Mann-Whitney
test; P = 0.02, Fisher's exact test), but there was no significant difference in
IGF-1R. TUNEL results showed no significant differences between groups. Our
results suggest that clinical and functional differences between alternative
forms of EWS-FLI1 are paralleled by differences in proliferative rate, possibly
mediated by differential regulation of the IGF-1R pathway
Osteoblastoma: varied histological presentations but with a benign clinical course: an analysis of 55 cases.
The presence of epithelioid osteoblasts, lace- or sheet-like osteoid production, and a permeative pattern of tumor growth in osteoblastomas is thought to be associated with an aggressive clinical behaviour. This study assessed the prognostic significance of these and other histologic parameters by analyzing a large group of cases. Histologic material obtained from 55 patients who had osteoblastoma diagnosed and treated at Memorial Sloan-Kettering Cancer Center was analyzed. Additionally, the radiographic images were studied and the lesions were radiologically staged as stage 1 (quiescent), stage 2 (active), or stage 3 (aggressive). Epithelioid osteoblasts were detected in 14% of the cases without any mitotic activity. Lace- or sheet-like osteoid was present in 36% of the cases studied. A permeative pattern of tumor growth was present in 15% of lesions in all but one arising in the short tubular or large flat bones. Thirty-four percent of the lesion were in stage 1, 48% in stage 2, and 17% in stage 3. All stage 1 tumors involved long tubular bones, whereas all stage 3 tumors arose in the short tubular or flat bones. Local recurrence was noted in 16% of patients, all of whom had stage 2 lesions. One patient with a vertebral tumor eventually died with persistent disease. No association between the histologic features and disease outcome was demonstrated. The clinically aggressive behavior of osteoblastoma is not related to particular histologic features, but rather to the skeletal location. Mitotic activity is not present in osteoblasts in the osteoblastoma
Treatment algorithm for locally recurrent osteosarcoma based on local disease-free interval and the presence of lung metastasis
10.1002/cncr.22197Cancer10771607-1616CANC
Elevated physiologic tumor pressure promotes proliferation and chemosensitivity in human osteosarcoma
10.1158/1078-0432.CCR-04-2048Clinical Cancer Research1162389-239
Tumour interstitial fluid pressure may regulate angiogenic factors in osteosarcoma
Annals of the Academy of Medicine Singapore38121041-104