Quantification of angiogenesis in solid human tumours: an international consensus on the methodology and criteria of evaluation

Vermeulen, P; Gasparini, Giampietro; Fox, Stephen B.; Toi, Masakazu; Martín, L; McCulloch, Peter; Pezzella, Francesco; Viale, Giuseppe; Weidner, Noel; Harris, Adrian L.; Dirix, L.

doi:10.1016/s0959-8049(96)00379-6

Cited by 656 publications

(553 citation statements)

References 53 publications

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“…in selected regions with elevated vascular density (Weidner et al, 1991;Vermeulen et al, 1996). The discrepancy between our study and these studies cannot be attributed to the use of different procedures for assessment of vascular density either.…”

Section: Discussioncontrasting

confidence: 86%

“…Since then, similar correlations have been observed in a variety of histological types of human cancer (Weidner, 1993(Weidner, , 1995, leading to the suggestion that the rate of angiogenesis may be an independent prognostic indicator in malignant diseases (Vermeulen et al, 1996). In accordance with this suggestion, recent studies of squamous cell carcinoma of the uterine cervix have shown that high vascular density in the primary tumour is correlated with vascular space invasion, lymphatic involvement and pelvic lymph node metastasis (Wiggins et al, 1995;Bremer et al, 1996;Hawighorst et al, 1997), and may predict low recurrence-free and overall survival probabilities (Schlenger et al, 1995).…”

mentioning

confidence: 57%

“…Recent studies involving several histogical types of human cancer, including squamous cell carcinoma of the uterine cervix, have suggested that high vascular density in the primary tumour is associated with a high incidence of metastases (Weidner, 1995;Wiggins et al, 1995;Bremer et al, 1996;Vermeulen et al, 1996;Hawighorst et al, 1997). Other studies, apparently inconsistent British Journal of Cancer (1998) Mean vascular density (number per mm2) Figure 3 Maximum vascular density vs mean vascular density in the primary tumour of patients with squamous cell carcinoma of the uterine cervix.…”

Section: Discussionmentioning

confidence: 99%

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Tumour hypoxia and vascular density as predictors of metastasis in squamous cell carcinoma of the uterine cervix

Sundfør

Lyng²,

Rofstad³

1998

Br J Cancer

169

106

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Summary Some clinical studies involving several histological types of cancer have suggested that high vascular density in the primary tumour promotes metastasis. Other studies have suggested that a high incidence of metastases is associated with low oxygen tension in the primary tumour. The purpose of the study reported here was to search for correlations between incidence of metastases and oxygen tension or vascular density in the same population of patients. Thirty-eight consecutive patients with squamous cell carcinoma of the uterine cervix were included in a prospective study. Pelvic, iliac and retroperitoneal lymph node metastases were detected by magnetic resonance imaging at the time of initial diagnosis. Oxygen tension was measured polarographically using the Eppendorf P02 Histograph 6650. Vascular density was determined by histological examination of tumour biopsies. The primary tumours of the patients with metastases (n = 19) were more poorly oxygenated than those of the patients without metastases (n = 19). Thus, the fractions of the P02 readings resulting in values below 5 mmHg and 10 mmHg were significantly higher for the former group of patients than for the latter (P = 0.03 and 0.02 respectively). In contrast, the vascular density of the primary tumour was not significantly different for the two groups of patients. The present study suggests that a high incidence of metastases in squamous cell carcinoma of the uterine cervix is associated with poor oxygenation of the primary tumour and not with a high vascular density.

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Section: Discussioncontrasting

confidence: 86%

mentioning

confidence: 57%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Tumour hypoxia and vascular density as predictors of metastasis in squamous cell carcinoma of the uterine cervix

Sundfør

Lyng²,

Rofstad³

1998

Br J Cancer

169

106

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“…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. But as CD34 has been shown to yield higher microvessel values than CD31 or factor VIII in breast cancer (Martin et al, 1997), it might be useful to combine CD34 and CD31 antibodies.…”

Section: Discussionmentioning

confidence: 99%

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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“…We regarded as a distinct countable microvessel any highlighted endothelial cell or cell cluster clearly separated from adjacent microvessels, tumour cells, normal cells and other connective tissue elements according to the international consensus (Vermeulen et al, 1996).…”

Section: Evaluation Of Vascularitymentioning

confidence: 99%

Vascular patterns in reactive lymphoid tissue and in non-Hodgkin's lymphoma

et al. 2003

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The few studies published on angiogenesis in lymphoma have raised the question of whether or not microvessel density (MVD) is associated with more aggressive disease and have reported the observation that in follicular lymphomas, vessels are mature rather than immature. We investigated MVD and the vascular phenotype within follicular or diffuse large B-cell lymphomas, reactive nodes and tonsils. Vascular phenotype was defined by the expression or loss of reactivity to the antibody LH39 (detecting the LH39 laminin epitope of the basement membrane in mature vessels) and by detection of aVb3 (expressed on immature vessels). In reactive nodes and in follicular lymphomas, MVD was higher in the paracortex than in germinal centres or in neoplastic follicles. However, in neoplastic follicles an increase in aVb3-positive endothelium suggested the activation of an angiogenic pathway different from that present in the reactive follicles. In large B-cell lymphomas, MVD was higher than in reactive and neoplastic follicles but lower than in the reactive paracortex. The number of immature vessels (LH39 negative) and of aVb3-positive vessels was higher than in reactive lymph nodes and follicular lymphoma suggesting that a switch to a different angiogenic pathway has occurred. Finally, we have demonstrated that within reactive and neoplastic follicles vascular regression is occurring, perhaps constraining the growth of reactive follicles alongside other phenomena such as apoptosis. Vascular regression was previously believed to occur in adults only in ovarian and endometrial tissue. We conclude that different types of angiogenesis are present in follicular lymphomas and large B-cell lymphomas. This has implications for possible future therapies.

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Quantification of angiogenesis in solid human tumours: an international consensus on the methodology and criteria of evaluation

Cited by 656 publications

References 53 publications

Tumour hypoxia and vascular density as predictors of metastasis in squamous cell carcinoma of the uterine cervix

Tumour hypoxia and vascular density as predictors of metastasis in squamous cell carcinoma of the uterine cervix

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

Vascular patterns in reactive lymphoid tissue and in non-Hodgkin's lymphoma

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