Preclinical Study

Breast Cancer Research and Treatment

, Volume 133, Issue 2, pp 501-510

Vascular proliferation is a prognostic factor in breast cancer

  • Jarle B. ArnesAffiliated withSection for Pathology, The Gade Institute, University of Bergen, Haukeland University Hospital
  • , Ingunn M. StefanssonAffiliated withSection for Pathology, The Gade Institute, University of Bergen, Haukeland University Hospital
  • , Oddbjørn StraumeAffiliated withSection for Pathology, The Gade Institute, University of Bergen, Haukeland University Hospital
  • , Jan P. BaakAffiliated withDepartment of Pathology, Stavanger University HospitalThe Gade Institute, University of BergenFree University
  • , Per E. LønningAffiliated withSection of Oncology, Institute of Medicine, University of BergenDepartment of Oncology, Haukeland University Hospital
  • , William D. FoulkesAffiliated withSection for Pathology, The Gade Institute, University of Bergen, Haukeland University HospitalHôpital du Sacré-Coeur de MontréalProgram in Cancer Genetics, Departments of Oncology and Human Genetics, McGill UniversitySegal Cancer Centre, Jewish General HospitalMcGill University
  • , Lars A. AkslenAffiliated withSection for Pathology, The Gade Institute, University of Bergen, Haukeland University Hospital Email author 

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Abstract

Angiogenesis is important for the growth and spread of malignant tumors, and anti-angiogenesis treatment is currently being evaluated for breast cancer and other tumors. Although microvessel density is the most commonly used tissue-based marker of tumor associated angiogenesis, it has significant limitations and has not proven effective as a predictive factor in selecting patients for treatment. We here wanted to explore the significance of vascular endothelial cell proliferation in breast carcinoma. We examined microvessel proliferation in breast cancer by dual immunohistochemical staining, using the pan-endothelial marker Factor-VIII combined with proliferation of endothelial cells by Ki-67 expression, in three independent series of breast cancer, including a total of 499 patients and 141 events during follow-up. Common statistical tests of associations as well as univariate and multivariate regression analysis of patient survival were used. By counting vessels with actively proliferating endothelium, we show that microvascular proliferation is a significant predictor of disease progression in breast cancer, especially among high-grade and ER-negative tumors. Our findings indicate that this novel marker of active tumor angiogenesis might be of value in patient management and should be further studied in the context of patient selection for anti-angiogenesis treatment.

Keywords

Breast cancer Angiogenesis Vascular proliferation Prognosis