Angiogenesis, assessed by platelet/endothelial cell adhesion molecule antibodies, as indicator of node metastases and survival in breast cancer

Horak, E.; Klenk, Nicola; Leek, Russell; Lejeune, Sue; Smith, Kelly J.; Stuart, N. S. A.; Harris, Adrian L.; Greenall, Michael J.; Stepniewska, Kasia

doi:10.1016/0140-6736(92)93150-l

Cited by 748 publications

(407 citation statements)

References 16 publications

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“…JC70 antibody stains also CD31 positive lymphocytes that could be a prognostically important inflammatory component in lung cancer . For some authors, CD31 seems to be the most sensitive marker for the endothelial cells and consistently stains more vessels than did factor VIII (Horak et al, 1992). An international consensus on the methodology and criteria of evaluation of microvessel density proposed that anti-CD31 monoclonal antibody should be the standard for microvessel assessment (Vermeulen et al, 1996) as it is superior on paraffin sections.…”

Section: Discussionmentioning

confidence: 96%

The role of microvessel density on the survival of patients with lung cancer: a systematic review of the literature with meta-analysis

et al. 2002

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In order to determine whether angiogenesis is a prognostic marker in lung cancer, we performed a systematic review of the literature to assess the prognostic value on survival of microvessel count in patients with lung cancer. Published studies were identified by an electronic search in order to aggregate survival results, after a methodological assessment using a quality scale designed by the European Lung Cancer Working Party. To be eligible, a study had to deal with microvessel count assessment in lung cancer patients on the primary site and to provide survival analysis according to microvessel count expression. Microvessel count has been assessed on surgical samples by immunohistochemistry using factor VIII in 14 studies, CD34 in 10 and CD31 in eight. Respectively 1866, 1440 and 1093 non-small cell lung cancer patients were considered. The overall median quality scores were respectively 52, 59 and 59% for studies assessing microvessel count via factor VIII, CD34 and CD31, without significant difference between studies evaluable or not for meta-analysis nor between studies with significant or non significant results. Seven 'factor VIII' studies, nine 'CD34' and seven 'CD31' provided sufficient data allowing a metaanalysis on survival and were evaluable for results aggregation. This showed that a high microvessel count in the primitive lung tumour was a statistically significant poor prognostic factor for survival in non small cell lung cancer whatever it was assessed by factor VIII (HR: 1.81; 95% CI: 1.16 -2.84), CD34 (HR: 1.99; 95% CI: 1.53 -2.58) or CD31 (HR: 1.80; 95% CI: 1.10 -2.96). Variations in survival among the individual studies can be explained in addition to patients selection criteria by the heterogeneous methodologies used to stain and count microvessels: different antibody clones, identification of 'hotspots', Weidner or Chalkey counting method, cut-off selection. Microvessel count, reflecting the angiogenesis, appears to be a poor prognostic factor for survival in surgically treated non small cell lung cancer but standardisation of angiogenesis assessment by the microvessel count is necessary.

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Section: Discussionmentioning

confidence: 96%

The role of microvessel density on the survival of patients with lung cancer: a systematic review of the literature with meta-analysis

et al. 2002

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“…Only CD3 1, CD34 and factor VIII-related antigen are available for staining formalin-fixed endothelial cells (Fina et al, 1990;Parums et al, 1990;Schlingemann et al, 1990). Based on a review of the literature we chose JC70, an anti-CD31 antibody, as marker for the microvessels as this endothelial marker is the most sensitive and specific of all and it does not react with lymphatic endothelium (Parums et al, 1990;Horak et al, 1992;Kuzu et al, 1992). However, of the seven previously published studies about invasive cervical cancer and angiogenesis, six used factor VIII (Kainz et al, 1995;Rutgers et al, 1995;Schlenger et al, 1995;Wiggens et al, 1995;Dinh et al, 1996;Abulafia et al, 1996), one Ulex europeaus lectin I (Bremer et al, 1996) and none CD31 as endothelial marker.…”

Section: Discussionmentioning

confidence: 99%

“…Microvessels can be visualized by specifically immunostaining the endothelial cells. The most sensitive antibody to formalinresistant endothelial antigen is the cell surface marker CD31 (Parums et al, 1990;Horak et al, 1992). CD31 is a member of the adhesion molecule family and is also known as plateletendothelial cell adhesion molecule-1 (PECAM-1) or endothelial cell adhesion molecule (endoCAM-1) (Newman et al, 1990;Parums et al, 1990).…”

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confidence: 99%

Quantification and prognostic relevance of angiogenic parameters in invasive cervical cancer

Tjalma

Marck²,

Weyler³

et al. 1998

Br J Cancer

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Summary Tumour stromal neovascularization was investigated in 114 invasive and 20 in situ carcinomas of the uterine cervix by staining representative sections with the specific endothelial marker anti CD31 (clone JC/70A, isotope IgG1). A digital image analyser was used to measure the immunoreactivity. The following parameters were determined in the 'hot spots': vessel counts, vessel perimeter and endothelial stained area (expressed per mm2). The results were correlated with clinical and histopathological data. There was no significant relationship between the histopathological findings (tumour histology, tumour differentiation, FIGO stage, presence of lymph node metastasis or lymphovascular space involvement) and the median vessel count. In a univariate analysis all angiogenesis parameters had prognostic value: a higher vascularity was associated with worse prognosis (P < 0.05). Multiple regression analysis showed that vascular permeation (P < 0.001) and the median vessel count (P = 0.005) were the most important prognostic indicators. In the future these criteria may be used for selection of patients for anti-angiogenesis therapy.

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“…For immunohistochemistry, a murine monoclonal antibody (mAb) against murine CD31 (clone 1A10, Dako, Glostrup, Denmark), a more sensitive endothelial cell marker than factor VIII antigen (Horak et al, 1992), was used. Briefly, sections were collected on 3-aminopropyl-triethoxysilane-coated slides, deparaffinised by the xylene -ethanol sequence, rehydrated in a graded ethanol scale and in Tris-buffered saline (TBS, pH 7.6) and incubated overnight at 41C with the mAb 1A10 (1 : 25 in TBS), after antigen retrieval by enzymatic digestion with Ficin (Sigma, St Louis, MO, USA) for 30 min at room temperature.…”

Section: Immunohistochemical Studymentioning

confidence: 99%

Angiogenesis in a human neuroblastoma xenograft model: mechanisms and inhibition by tumour-derived interferon-γ

et al. 2006

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Tumour progression in neuroblastoma (NB) patients correlates with high vascular index. We have previously shown that the ACN NB cell line is tumorigenic and angiogenic in immunodeficient mice, and that interferon-g (IFN-g) gene transfer dampens ACN tumorigenicity. As IFN-g represses lymphocyte-induced tumour angiogenesis in various murine models and inhibits proliferation and migration of human endothelial cells, we have investigated the antiangiogenic activity of tumour-derived IFN-g and the underlying mechanism(s). In addition, we characterised the tumour vasculature of the ACN xenografts, using the chick embryo chorioallantoic membrane assay. We show that the ACN/IFN-g xenografts had a lower microvessel density and less in vivo angiogenic potential than the vector-transfected ACN/neo. The vascular channels of both xenografts were formed by a mixed endothelial cell population of murine and human origin, as assessed by the FICTION (fluorescence immunophenotyping and interphase cytogenetics) technique. With respect to ACN/neo, the ACN/IFN-g xenografts showed more terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling-positive human and murine endothelial cells, suggesting that inhibition of angiogenesis by IFN-g was dependent on the induction of apoptosis, likely mediated by nitric oxide. Once the dual origin of tumour vasculature is confirmed in NB patients, the xenograft model described here will prove useful in testing the efficacy of different antiangiogenic compounds.

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Angiogenesis, assessed by platelet/endothelial cell adhesion molecule antibodies, as indicator of node metastases and survival in breast cancer

Cited by 748 publications

References 16 publications

The role of microvessel density on the survival of patients with lung cancer: a systematic review of the literature with meta-analysis

The role of microvessel density on the survival of patients with lung cancer: a systematic review of the literature with meta-analysis

Quantification and prognostic relevance of angiogenic parameters in invasive cervical cancer

Angiogenesis in a human neuroblastoma xenograft model: mechanisms and inhibition by tumour-derived interferon-γ

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