Microvessel Density as Determined by Computerized Image Analysis of CD105 Expression Correlates with Clinicopathological Features and Outcome in Triple-Negative Breast Cancer
Marina De Brot, Rafael M Rocha, Fernando A Soares, Helenice Gobbi. Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; AC Camargo Hospital, Sao Paulo, Brazil
Background: Triple-negative breast cancers (TNBCs) tend to relapse and metastasize early with a distinct pattern of dissemination. Although the occurrence of metastasis is related to angiogenesis, literature on angiogenic characteristics of these tumors is limited. We assessed topography and characteristics of blood vessels in TNBC and examined their association(s) with clinicopathological criteria, basal-like phenotype and prognosis in a series of TNBCs.
Design: Clinicopathological data were obtained from 133 TNBCs. For identification of blood vessels, FFPE whole tissue sections were stained with CD105; slides were scanned using Aperio Digital Pathology System. Each digital slide was examined by a pathologist and divided into three regions: intratumoral (IT), peripheral (PP) and peritumoral (PT) areas. Three hot spots were selected in each region (IT, PP, PT - area of 6.0 mm2 each). Microvessel density (MVD) was measured by applying the Microvessel Density v1 algorithm. MVD was categorized into high MVD and low MVD according to its median value. Associations between MVD in each region and clinicopathological criteria were evaluated in univariate and multivariate analysis.
Results: Median time of follow-up was 40 months (range, 1-161 months). In all, 53 (39.1%) patients had developed a recurrence by the time of last follow-up; distant metastasis was detected in 49 (36.8%) patients, lungs, brain and bones representing the main sites. Overall, 101 (75.9%) TNBCs showed a basal-like phenotype. Blood vessels were located largely in the peripheral area; TNBCs with a basal phenotype showed higher MVDs (p=0.028). A significant association was observed between high peripheral MVD, recurrence (p=0.038) and development of distant metastasis (p=0.031). High peritumoral MVD was associated with vascular invasion (p=0.015). Survival analysis showed that high peripheral MVD was strongly associated with poorer overall survival (OS, p=0.001) and disease-free interval (DFI, p=0.001). In multivariate analysis for OS and DFI, peripheral MVD retained its prognostic significance (p= 0.003) after adjustment for significant variables (stage and lymph node status).
Conclusions: We demonstrate associations between MVD in different areas and various parameters in TNBCs, indicating that tumors with aggressive features have higher MVDs. Neovessels are mainly located in the peripheral area of TNBCs and may have a critical role in disease dissemination.
Tuesday, March 5, 2013 9:30 AM
Poster Session III # 19, Tuesday Morning