1. ¹Department of Obstetrics and Gynecology, University of Münster, Albert-Schweitzer-Str. 33, 48129 Münster, Germany
2. ²Gerhard-Domagk-Institute of Pathology, University of Münster, Albert-Schweitzer-Str. 33, 48129 Münster, Germany
3. ³Department of Hematology and Oncology, University of Münster, Albert-Schweitzer-Str. 33, 48129 Münster, Germany
4. ⁴Institut für Pathologie, St Vincenz-Krankenhaus Limburg, Germany
5. ⁵Institut für Pathologie, Köln-Rodenkirchen, Germany

Correspondence: Dr P Wülfing, E-mail: wuelfip@uni-muenster.de

⁶Shared first authorship

Received 10 November 2004; Accepted 10 March 2005; Published online 19 April 2005.

Abstract

The objective of this study was to investigate expression of various growth factors associated with angiogenesis and lymphangiogenesis and of their receptors in ductal carcinomas in situ of the breast (DCIS). We studied protein expression of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF)-A, endothelin (ET)-1, and VEGF-C, and their receptors bFGF-R1, Flt-1, KDR, ET_AR, ET_BR, and Flt-4 immunohistochemically in 200 DCIS (pure DCIS: n=96; DCIS adjacent to an invasive component: n=104) using self-constructed tissue microarrays. Basic fibroblast growth factor-R1, VEGF-C, Flt-4, and ET_AR were expressed in the tumour cells in the majority of cases, whereas bFGF and Flt-1 expression was rarely observed. VEGF-A, KDR, ET-1, and ET_BR were variably expressed. The findings of VEGF-C and its receptor Flt-4 as lymphangiogenic factors being expressed in tumour cells of nearly all DCIS lesions and the observed expression of various angiogenic growth factors in most DCIS suggest that in situ carcinomas are capable of inducing angiogenesis and lymphangiogenesis. Moreover, we found a higher angiogenic activity in pure DCIS as compared to DCIS with concomitant invasive carcinoma. This association of angiogenic factors with pure DCIS was considerably more pronounced in the subgroup of non-high-grade DCIS (n=103) as compared with high-grade DCIS (n=94). Determination of these angiogenic markers may therefore facilitate discrimination between biologically different subgroups of DCIS and could help to identify a particularly angiogenic subset with a potentially higher probability of recurrence or of progression to invasiveness. For these DCIS, targeting angiogenesis may represent a feasible therapeutic approach for prevention of progression of DCIS to invasion.