Lack of Prognostic Significance of Intratumoral Angiogenesis in Nonmetastatic Osteosarcoma

Mantadakis, Elpis; Kim, Grace; Reisch, Joan; McHard, D. Kim; Maale, Gerhard E.; Leavey, Patrick J.; Timmons, Charles F.

doi:10.1097/00043426-200106000-00010

Cited by 37 publications

(30 citation statements)

References 31 publications

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“…A smaller series of 29 pediatric patients with nonmetastatic osteosarcoma treated at a single institution evaluated microvessel density using CD34 staining. 30 Microvessel density did not differ between patients who survived and patients who died from osteosarcoma. These 3 conflicting reports highlight the difficulty in drawing conclusions from subjective measures of angiogenesis, particularly in the setting of different microvessel stains between studies.…”

Section: Skeletal Sarcomasmentioning

confidence: 85%

Markers of angiogenesis and clinical features in patients with sarcoma

DuBois

Demetri

2007

Cancer

129

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Objective: Patient outcome after traumatic brain injury (TBI) is highly variable. The underlying pathophysiology of this is poorly understood, but inflammation is potentially an important factor. Microglia orchestrate many aspects of this response. Their activation can be studied in vivo using the positron emission tomography (PET) ligand [11C](R)PK11195 (PK). In this study, we investigate whether an inflammatory response to TBI persists, and whether this response relates to structural brain abnormalities and cognitive function. Methods: Ten patients, studied at least 11 months after moderate to severe TBI, underwent PK PET and structural magnetic resonance imaging (including diffusion tensor imaging). PK binding potentials were calculated in and around the site of focal brain damage, and in selected distant and subcortical brain regions. Standardized neuropsychological tests were administered. Results: PK binding was significantly raised in the thalami, putamen, occipital cortices, and posterior limb of the internal capsules after TBI. There was no increase in PK binding at the original site of focal brain injury. High PK binding in the thalamus was associated with more severe cognitive impairment, although binding was not correlated with either the time since the injury or the extent of structural brain damage. Interpretation: We demonstrate that increased microglial activation can be present up to 17 years after TBI. This suggests that TBI triggers a chronic inflammatory response particularly in subcortical regions. This highlights the importance of considering the response to TBI as evolving over time and suggests interventions may be beneficial for longer intervals after trauma than previously assumed. ANN NEUROL 2011;

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Section: Skeletal Sarcomasmentioning

confidence: 85%

Markers of angiogenesis and clinical features in patients with sarcoma

DuBois

Demetri

2007

Cancer

129

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“…Numerous studies have indicated that VD may be of Unlike carcinomas, the situation is less clear for sarcomas where VD may not correlate with outcome. [29][30][31][32] However, our preliminary examination of VD in 29 osteosarcoma samples neither revealed any correlation with tumor progression (primary vs metastasis) nor with vWF expression. The lack of correlation between VD and vWF expression is not surprising given that vWF expression is affected by numerous factors including vessel type and size, tissue microenvironment, and angiogenic factors.…”

Section: Discussionmentioning

confidence: 99%

von Willebrand factor expression in osteosarcoma metastasis

et al. 2005

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A number of genes are implicated in the initiation and progression of osteosarcoma; however, cytogenetic and comparative genomic hybridization studies indicate the involvement of additional unidentified genes. An examination of gene expression profiles in 22 high-grade osteosarcoma tumor specimens from 15 patients (including paired primary and metastatic samples from five patients) indicated that von Willebrand factor (vWF) mRNA expression may increase during tumor progression. vWF, a large glycoprotein previously considered to be expressed exclusively by endothelial cells and megakaryocytes, is involved in platelet aggregation and adhesion to the subendothelial matrix, processes critical to hematogenous tumor cell metastasis to the lung. Analysis of paired primary and metastatic osteosarcoma tumor samples from 10 patients revealed an increase in vWF gene expression in metastases (P ¼ 0.005). Immunohistochemistry showed that, in addition to the endothelial cells, vWF protein was also detected in osteosarcoma cells in vivo in 13 of 29 tumor specimens as well as in SAOS2, an osteosarcoma cell line. The tumor cell staining correlated positively with high vWF expression in the sample (P ¼ 0.006). Although vascular endothelial cells contribute to the vWF mRNA detected in the tumor samples, there was neither any correlation between vascular density (VD) and vWF mRNA expression nor between VD and clinical outcome. These findings suggest that vWF expression is deregulated in osteosarcoma tumors, potentially contributing to metastasis.

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“…This exclusion was performed due to incongruent data on the prognosis of these patients (21)(22)(23)(24). Moreover, another study excluded patients with chondroblastic osteosarcoma because cartilaginous stroma was described to be associated with hypovascularity (8).…”

Section: Resultsmentioning

confidence: 99%

“…However, the role of angiogenesis in osteosarcoma still remains a matter of debate. Whereas one report by Wang et al (7) showed evidence for decreased overall survival in osteosarcoma patients with high MVD, Mantadakis et al (8) failed to demonstrate a correlation between intratumoral neovascularization and long-term outcome in patients with nonmetastatic osteosarcoma. Experimental studies on the role of tumor MVDs revealed a significant correlation between MVD and pulmonary metastasis (9).…”

Section: Introductionmentioning

confidence: 97%

Prognostic Relevance of Increased Angiogenesis in Osteosarcoma

Kreuter

Bieker

Bielack

et al. 2004

Clinical Cancer Research

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Purpose: The purpose of this work was to evaluate the prognostic relevance of microvessel density (MVD) for response to chemotherapy and long-term outcome in osteosarcoma.Experimental Design: Pretherapeutic tumor biopsies of 60 patients with high-grade central osteosarcoma, who were treated according to multimodal neoadjuvant protocols of the German-Austrian-Swiss Cooperative Osteosarcoma Study Group, were evaluated for intratumoral MVD. MVD was correlated with demographic and tumor-related variables, response, and survival.Results: The median intratumoral MVD was 52 microvessels per 0.26-mm 2 field area (interquartile range, 31-77 microvessels per 0.26-mm 2 field area). At a median follow-up period of 3.5 years, patients with a high (>me-dian) MVD had significantly higher 5-and 10-year overall survival rates (84%) than patients with low (

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Lack of Prognostic Significance of Intratumoral Angiogenesis in Nonmetastatic Osteosarcoma

Abstract: Intratumoral neovascularization determined at diagnosis does not correlate with long-term outcome in patients with nonmetastatic osteosarcoma. A prospective study is necessary to confirm these results.

Cited by 37 publications

References 31 publications

Markers of angiogenesis and clinical features in patients with sarcoma

Markers of angiogenesis and clinical features in patients with sarcoma

von Willebrand factor expression in osteosarcoma metastasis

Prognostic Relevance of Increased Angiogenesis in Osteosarcoma

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