Relationship between vascularity, age and survival in non-small-cell lung cancer

Chandrachud, Lata M.; Pendleton, Neil; Chisholm, D. M.; Horan, Michael A.; Schor, Ana M.

doi:10.1038/bjc.1997.562

Cited by 58 publications

(46 citation statements)

References 29 publications

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“…Information related to the tumours analysed is given in Table 1. All tumour blocks were selected on the basis of containing ample and representative tumour areas in haematoxylin and eosin (H&E) sections as described (Chandrachud et al, 1997).…”

Section: Materials and Methods Specimensmentioning

confidence: 99%

Heterogeneity in microvascular density in lung tumours: comparison with normal bronchus

Schor

Pazouki²,

Morris³

et al. 1998

Br J Cancer

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Summary The aim of this study was to test the hypotheses that (a) microvascular density (MVD) measured in histological sections of resected non-small cell lung carcinomas is an index of angiogenesis and (b) the measurement of MVD in a single block is representative of the overall MVD of the tumour. MVD was quantitated in one block per specimen of 60 lung tumours and nine normal lung tissues, and in 47 blocks taken from different regions of four tumours. Blood vessels were stained with antibody to von Willebrand Factor and MVD was quantitated using two methods: average density throughout the section (a-MVD) and density in the most vascularized area or 'hot spot' (h-MVD). Similar h-MVD values were found in tumours and in normal bronchus, whereas a-MVD was greater in the latter (P < 0.01). When 47 blocks from four tumours were analysed, inter-tumour variation was significant (P < 0.001) in spite of significant intra-tumour variation. The highest MVD value was not necessarily found in the periphery of the tumour. The four tumours were ranked into either two or four tiers according to their overall MVD. In 50 random selections of one block per tumour, the correct ranking was achieved in 68-74% of cases with the two-tier ranking and in 6-16% of cases with the four-tier ranking (h-MVD and a-MVD values respectively). These results suggest that elevated MVD values do not necessarily represent angiogenesis in non-small cell lung carcinomas. When only one block per tumour is examined, the chance of obtaining an accurate estimate of the vascularity of that tumour may be lower than 68%.

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Section: Materials and Methods Specimensmentioning

confidence: 99%

Heterogeneity in microvascular density in lung tumours: comparison with normal bronchus

Schor

Pazouki²,

Morris³

et al. 1998

Br J Cancer

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“…In the 14 remaining eligible studies (Macchiarini et al, 1994;Yamazaki et al, 1994;Fontanini et al, 1995;Mattern et al, 1995;Chandrachud et al, 1997;Giatromanolaki et al, 1997;Takanami et al, 1997;Duarte et al, 1998;Imoto et al, 1998;Aikawa et al, 1999;D'Amico et al, 1999;Ohta et al, 1999;Sheng et al, 2000;Yano et al, 2000), published between 1994 and 2000, the total number of patients was 1866 ranging from 28 to 408. The main characteristics of these 14 studies are shown in Table 1.…”

Section: Studies Selection and Characteristicsmentioning

confidence: 99%

“…Microvessel density seems to be an important prognostic indicator in lung cancer (Fontanini et al, 1995;Giatromanolaki et al, 1997) although some studies have not found microvessel count to be predictive for survival (Chandrachud et al, 1997;Pastorino et al, 1997). Currently, different antibodies to three endothelial cell antigens can be used to visualise the tumour blood vessels by immunohistochemistry: factor VIII antigen or von Willebrand's factor is involved in platelet adhesion and aggregation; CD31 or PECAM 1 (platelet/endothelial cell adhesion molecule) is associated with platelet adhesion in inflammation, wound healing, trans-endothelial cell migration and cell migration; CD34 is involved in leukocyte adhesion and endothelial cell migration during angiogenesis.…”

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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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“…It is likely that the difficulties with this method have lead to a substantial number of studies in which no correlation (Brechot et al, 1996;Chandrachud et al, 1997;Hillen et al, 1997) or even an inverse correlation (Sarbia et al, 1996;Delahunt et al, 1997) was found between angiogenesis and the aggressiveness of the tumour. This urged researchers to quantify MVD by using image-analysis software (Kirchner et al, 1996;Wild et al, 2000;).…”

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confidence: 99%

Flow cytometric quantification of tumour endothelial cells; an objective alternative for microvessel density assessment

et al. 2002

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Assessment of microvessel density by immunohistochemical staining is subject to a considerable inter-observer variation, and this has led to variability in correlation between microvessel density and clinical outcome in different studies. In order to improve the method of microvessel density measurement in tumour biopsies, we have developed a rapid, objective and quantitative method using flow cytometry on frozen tissues. Frozen tissue sections of archival tumour material were enzymatically digested. The single-cell suspension was stained for CD31 and CD34 for flow cytometry. The number of endothelial cells was quantified using light scatter-and fluorescence-characteristics. Tumour endothelial cells were detectable in a single cell suspension, and the percentage of endothelial cells detected in 32 colon carcinomas correlated highly (r=0.84, P50.001) with the immunohistochemical assessment of microvessel density. Flow cytometric endothelial cells quantification was found to be more sensitive especially at lower levels of immunohistochemical microvessel density measurement. The current method was found to be applicable for various tumour types and has the major advantage that it provides a retrospective and quantitative approach to the angiogenic potential of tumours. British Journal of Cancer (2002) Angiogenesis is essential for the outgrowth of tumours and metastasis formation (Griffioen and Molema, 2000). It has been recognised that the angiogenic potential of a tumour contributes to the aggressiveness of that tumour and may therefore be of prognostic importance for various cancers. An increasing number of studies have demonstrated that angiogenesis is predictive for the clinical outcome of the disease, in the sense that an increased level of angiogenesis is inversely related with survival (Weidner et al, 1992(Weidner et al, , 1993. In most of these studies, the angiogenic potential was analysed by immunohistochemical determination of microvessel density (MVD) using antibodies recognising CD31, CD34 or Von Willebrand Factor. This method is currently considered the gold standard for this kind of studies. Although straightforward and routinely performed in most diagnostic laboratories the immunohistochemical MVD measurement has a number of disadvantages. The method is laborious, difficult to quantitate, and suffers from considerable intra-and inter-observer variation. This made an international agreement on performance of MVDanalysis necessary (Vermeulen et al, 1996).It is likely that the difficulties with this method have lead to a substantial number of studies in which no correlation (Brechot et al, 1996;Chandrachud et al, 1997;Hillen et al, 1997) or even an inverse correlation (Sarbia et al, 1996;Delahunt et al, 1997) was found between angiogenesis and the aggressiveness of the tumour. This urged researchers to quantify MVD by using image-analysis software (Kirchner et al, 1996;Wild et al, 2000;). Other methods to measure angiogenesis in patients include detection of circulating levels of angiogenic growth fa...

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Relationship between vascularity, age and survival in non-small-cell lung cancer

Cited by 58 publications

References 29 publications

Heterogeneity in microvascular density in lung tumours: comparison with normal bronchus

Heterogeneity in microvascular density in lung tumours: comparison with normal bronchus

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

Flow cytometric quantification of tumour endothelial cells; an objective alternative for microvessel density assessment

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