Tumour Angiogenesis as a Prognostic Marker in Infiltrating Lobular Carcinoma of the Breast

Morphopoulos, G; Pearson, Matthew; Ryder, W. David J.; Howell, Anthony; Harris, Martin

doi:10.1002/(sici)1096-9896(199609)180:1<44::aid-path648>3.0.co;2-c

Cited by 48 publications

(19 citation statements)

References 29 publications

(2 reference statements)

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“…In contrast to the results cited above, other studies have concluded that MVD has no predictive value (Carnochan et al, 1991;Hall et al, 1992;Van Hoef et al, 1993;Leedy et al, 1994;Axelsson et al, 1995;Mattem et al, 1995;Tahan et al, 1995;Morphopoulus et al, 1996). Although studies reporting a positive correlation outnumber those reporting no correlation (reviewed in Gasparini and Harris, 1995), it is also of interest that several studies found that high tumour MVD values were associated with good prognosis (Awwad et al, 1986;Delides et al, 1988;Revesz et al 1989;Kainz et al, 1995;Zatterstrom et al, 1995).…”

mentioning

confidence: 74%

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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mentioning

confidence: 74%

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

Schor

Pazouki²,

Morris³

et al. 1998

Br J Cancer

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“…There are several reports that do not demonstrate a relationship between IMD and survival (Hall et al, 1992;van Hoef et al, 1993;Axelsson et al, 1995;Costello et al, 1995;Goulding et al, 1995;Morphopoulos et al, 1996). While these studies may reflect a genuine biological finding there are a number of technical issues that may confound studies.…”

Section: Poor Associations Between Imd and Survivalmentioning

confidence: 99%

Intra-tumoural microvessel density in human solid tumours

2002

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Over the last decade assessment of angiogenesis has emerged as a potentially useful biological prognostic and predictive factor in human solid tumours. With the development of highly specific endothelial markers that can be assessed in histological archival specimens, several quantitative studies have been performed in various solid tumours. The majority of published studies have shown a positive correlation between intra-tumoural microvessel density, a measure of tumour angiogenesis, and prognosis in solid tumours. A minority of studies have not demonstrated an association and this may be attributed to significant differences in the methodologies employed for sample selection, immunostaining techniques, vessel counting and statistical analysis, although a number of biological differences may account for the discrepancy. In this review we evaluate the quantification of angiogenesis by immunohistochemistry, the relationship between tumour vascularity and metastasis, and the clinicopathological studies correlating intra-tumoral microvessel density with prognosis and response to anti-cancer therapy. In view of the extensive nature of this retrospective body of data, comparative studies are needed to identify the optimum technique and endothelial antigens (activated or pan-endothelial antigens) but subsequently prospective studies that allocate treatment on the basis of microvessel density are required. British Journal of Cancer (2002) Angiogenesis is the process in which new blood vessels arise from existing ones. This is present physiologically in the adult during wound healing, the development of the ovarian follicle and corpus luteum and in the proliferating endometrium. Pathological angiogenesis is also a component of much diverse pathology ranging from diabetes and atherosclerosis to cancer, a disease that cannot progress without the formation of new blood vessels (Folkman, 1972).The measurement of angiogenesis is complicated by the fact that it is a dynamic process yet most studies to date have focused on the product of angiogenesis, the microvessel density, which was analysed at a particular point in time. Accepting this caveat there are extensive data in which the microvessel density correlates with metastasis and survival. Here, we discuss the relationship between angiogenesis and the intra-tumoural microvessel density (IMD), review the different techniques that have been used to measure IMD and then discuss the reasons why this relationship does not always hold. IMD AS A MEASURE OF TUMOUR ANGIOGENESISAs angiogenesis is a dynamic process, comparisons with snapshot views of the tumour, as are seen in biopsy analyses, are not straightforward. On the other hand the only approaches that are available in the clinic for the serial measurement of tumour angiogenesis involve molecular imaging strategies, such as contrastenhanced magnetic resonance imaging (MRI) and positron emission tomography (PET), that do not resolve data at the microscopic level. Thus it is important to assess the relationship between IMD and...

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“…Much data suggest that the evaluation of the tumor angiogenic phenotype by immunohistochemical determination of microvessel density could have a prognostic value in different types of cancers [41], including breast cancers [5,13,18,40,42,43]. In contrast, other studies failed to demonstrate this hypothesis [1,2,8,16,17,26,28,29,33,37].…”

Section: Introductionmentioning

confidence: 99%

Assessment of tumor angiogenesis in invasive breast carcinomas: absence of correlation with prognosis and pathological factors

et al. 2000

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Different retrospective studies have shown that microvessel counting (MVC) is an independent prognostic marker for clinical outcome in breast cancer. The aim of this study was to evaluate the prognostic value of MVC alone or in association with classical clinicopathological parameters, as well as the reproducibility of the technique. We analyzed a retrospective series of 216 cases of breast carcinoma. Tissue sections were stained for Factor-VIII-related antigen. Microvessel quantification was performed at x400 magnification in the three most vascular areas of the tumors (hot spots). Mean and highest values were studied. Furthermore, a semi-quantitative evaluation of MVC was performed by use of an image-analysis system. The effect of multiple factors on survival was tested under a Cox multivariate proportional hazards model. In ten cases, a study of the reproducibility was done by evaluating MVC in different sections of the same block and in different blocks of a same tumor. There was no association between MVC (determined at a microscopic level or by image analysis) and overall survival or relapse-free survival. No association was found with tumor size, tumor grade, and lymph-node status. The study of reproducibility showed a very high intra-tumoral variation of MVC. The intra-individual coefficient of variation (CV) varied between 20 and 80%. This study did not show any significant correlation between angiogenesis, as assessed by MVC, and relapse-free survival or overall survival in infiltrating breast carcinomas. The low reproducibility of the MVC for the same tumors suggests that this technique must still be optimized before routine application.

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Tumour Angiogenesis as a Prognostic Marker in Infiltrating Lobular Carcinoma of the Breast

Cited by 48 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

Intra-tumoural microvessel density in human solid tumours

Assessment of tumor angiogenesis in invasive breast carcinomas: absence of correlation with prognosis and pathological factors

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