Histological quantitation of tumour angiogenesis

Abstract

Tumours establish their blood supply via a number of processes in addition to angiogenesis. These include vasculogenesis, vascular remodelling, intussusception and possibly vascular mimicry in certain tumours. The mainstay of the assessment of tumour vascularity has been counting the number of immunohistochemically identified microvessels in vascular hot spots. Nevertheless, several other techniques are available, including Chalkley counting, vascular grade and the use of image analysis systems. Angiogenic activity can furthermore be assessed in histological samples by measuring the molecules involved in the establishment of the tumour vasculature, including angiogenic growth factors and their receptors, cell adhesion molecules, proteases and markers of activated, proliferating, cytokine stimulated or angiogenic vessels, such as CD105. Measuring the maturity of vessels may give an indication of the proportion of the tumour vasculature that is functional. Other reagents that can identify hypoxia-activated pathways are also being developed. The histological assessment of tumour vascularity is mainly used in the research setting but may also have applications in the clinic if appropriate methodology and trained observers perform the studies. Gene arrays may be able to provide an angiogenesis profile. Continued study into the processes involved in generating a tumour blood supply is likely to identify new markers that may be more accurate measures.

Lymphatic and angiogenic characteristics in breast cancer: morphometric analysis and prognostic implications

“…They also stated that MVD is a significant, although weak, prognostic factor in breast cancer and that standardisation of MVD assessment is needed. Recommendations for such are mentioned in the review by Fox and Harris with regards the different methodologies used to assess angiogenesis [51].…”

Increased bone marrow microvascular density in haematological malignancies is associated with differential regulation of angiogenic factors

“…Its major limitation is that it usually involves a subjective selection of areas for microvessel enumeration and vessel evaluation. 23 Although computerized MVD evaluation has been developed, several limitations are also associated with this technology. 23 The grouping of different diagnoses might lead to the loss of important characteristics of separate diseases; and the separate sample sizes were limited as were the control groups.…”

“…23 Although computerized MVD evaluation has been developed, several limitations are also associated with this technology. 23 The grouping of different diagnoses might lead to the loss of important characteristics of separate diseases; and the separate sample sizes were limited as were the control groups. In addition, PBMNC contain different cell types, and the composition varies with the haematological malignancy according to whether malignant cells are present in peripheral blood.…”

Prognostic significance of vascular endothelial cell growth factors -A, -C and -D in breast cancer and their relationship with angio- and lymphangiogenesis

“…A 25-point Chalkley eyepiece graticule was applied to each hot spot and oriented to permit the maximum number of points to hit on, or within the areas of immunohistochemically highlighted microvessel using  200 magnification. A Chalkley count for an individual tumour was taken as the mean value of the three graticule counts (Fox and Harris, 2004).…”

“…The mainstay of assessment of tumour vascularity has been counting the number of immunohistochemically identified microvessels in vascular hot spots, known as the microvessel density (MVD) (Weidner et al, 1992), using vascular markers such as factor VIII-related antigen, CD34 and CD31, with a recent review recommending procedures that should be followed for the assessment of MVD in breast cancer (Fox and Harris, 2004). The assessment of lymphatic characteristics in malignant tumours has historically been difficult owing to the lack of availability of lymphatic-specific markers.…”