Microvessel Density as a Prognostic Factor in Women with Breast Cancer

Abstract

We performed a meta-analysis of all 87 published studies linking intratumoral microvessel density (MVD), reflecting angiogenesis, to relapse-free survival (RFS) and overall survival (OS). With median MVD as cutoff, MVD impact was measured by risk ratio (RR) between the two survival distributions. Seventeen studies did not mention survival data or fit inclusion criteria. Twenty-two were multiple publications of the same series, leaving 43 independent studies (8936 patients). MVD was assessed by immunohistochemistry, using antibodies against factor VIII (27 studies; n ‫؍‬ 5262), CD31 (10 studies; n ‫؍‬ 2296), or CD34 (8 studies; n ‫؍‬ 1726). MVD might be a better prognostic factor when assessed by CD31 or CD34 versus factor VIII (P ‫؍‬ 0.11). For RFS, statistical calculations were performed in 25 studies (6501 patients). High MVD significantly predicted poor survival [RR ‫؍‬ 1.54 for RFS and OS with the same 95% confidence interval (CI), 1.29 -1.84]. Twenty-two studies analyzed separately lymph node-negative patients (n ‫؍‬ 3580), for whom predictors of poor survival are requested. This latter meta-analysis included 15 studies for RFS (2727 patients) and 11 for OS (1926 patients). High MVD significantly predicted poor survival [RR ‫؍‬ 1.99 for RFS (95% CI, 1.33-2.98) and RR ‫؍‬ 1.54 for OS (95% CI, 1.01-2.33)]. Between-study variations could result from patient selection criteria, techniques to stain and count microvessels, and cutoff selection. MVD was a significant although weak prognostic factor in women with breast cancer. Standardization of MVD assessment is needed.

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

“…However, unlike their results, we could not find a significant association between high MVD and DFI or OS. In an interesting review, and meta-analysis, by Uzzan et al, examining 87 breast cancer angiogenesis studies; 25 reported significant association between MVD and DFI and 11 with OS [26]. The authors concluded that inter-study variation could result from patient selection criteria, staining techniques and methodology used in counting blood vessels and in selection of the cut-off level for MVD assessment.…”

“…It is now appreciated that angiogenesis has an important role in the progression of breast cancer, through providing essential nutrients for tumour cell growth and proliferation [23][24][25]. Microvessel density (MVD); as a measurement for angiogenesis, has been found to be strongly associated with features of tumour aggression as larger size and poor differentiation, however its role as a prognostic factor has not been firmly established [26].…”

In vivo MRI and histopathological assessment of tumor microenvironment in luminal‐like and basal‐like breast cancer xenografts

“…Dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) is used as a tool for in vivo characterization of tumor vasculature (10,11). Contrast enhancement kinetics obtained by DCE-MRI correlates with tumor type, histological grade, MVD, and biomarkers such as estrogen receptors (ER), progesterone receptors (PgR), and the proliferation marker Ki-67 (6,(12)(13)(14)(15)(16)(17). By using a pharmacokinetic two-compartment model, maps of tissue properties such as vascular permeability and perfusion (K trans ), extracellular extravascular volume fraction (v e ), and blood plasma volume fraction (v p ) can be obtained (18).…”

The influence of invasive growth pattern and microvessel density on prognosis in colorectal cancer and colorectal liver metastases

“…The assessment of microvessel density (MVD) is frequently used to quantify angiogenesis in archival tissue (Hlatky et al, 2002), although its use as a prognostic indictor is controversial. In breast cancer (Uzzan et al, 2004), non-small cell lung carcinoma (Ushijima et al, 2001) and melanoma (Ribatti et al, 2003), a high MVD is associated with poor outcome. In CRC, a high MVD has been shown to predict disease recurrence and survival in some studies (Saclarides et al, 1994;Tanigawa et al, 1997), whereas other studies have shown an association between high MVD and improved survival (Prall et al, 2003) or have concluded that MVD failed to provide additional prognostic information (Cianchi et al, 2002).…”