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Expression of vascular endothelial growth factor and vascular endothelial growth factor receptors 1 and 2 in invasive breast carcinoma: prognostic significance and relationship with markers for aggressiveness.

AbstractAIMS:
Vascular endothelial growth factor (VEGF), VEGF receptor 1 (VEGFR-1) and VEGF receptor 2 (VEGFR-2) play a role in breast cancer growth and angiogenesis. We examined the expression and relationship with clinical outcome and other prognostic factors.
METHODS AND RESULTS:
Tumour sections from 468 breast cancer patients were immunostained for VEGF, VEGFR-1, and VEGFR-2, and their relationships with tumour vascularity, disseminated tumour cells (DTCs) in bone marrow and other clinicopathological parameters were evaluated. VEGF, VEGFR-1 and VEGFR-2 immunoreactivities were observed in invasive breast carcinoma cells. VEGF expression was significantly associated with VEGFR-1 and VEGFR-2 expression (P < 0.001). High-level cytoplasmic expression of VEGFR-1 was associated with significantly reduced distant disease-free survival (DDFS) (P = 0.017, log-rank) and breast cancer-specific survival (BCSS) (P = 0.005, log-rank) for all patients, and for node-negative patients without systemic treatment (DDFS, P = 0.03, log-rank; BCSS, P = 0.009, log-rank). VEGFR-1 expression was significantly associated with histopathological markers of aggressiveness (P < 0.05). Significantly reduced survival was observed in DTC-positive patients as compared with DTC-negative patients in the combined moderate/high VEGFR-1 group (P < 0.001 for DDFS and BCSS), and the same was true for DDFS in the moderate VEGFR-2 group (P = 0.006).
CONCLUSIONS:
High-level expression of VEGFR-1 indicates reduced survival. Higher-level expression of VEGFR-1 or VEGFR-2 in primary breast carcinomas combined with the presence of DTC selects a prognostically unfavourable patient group.
AuthorsHari Prasad Dhakal, Bjørn Naume, Marit Synnestvedt, Elin Borgen, Rolf Kaaresen, Ellen Schlichting, Gro Wiedswang, Assia Bassarova, Ruth Holm, Karl-Erik Giercksky, Jahn M Nesland
JournalHistopathology (Histopathology) Vol. 61 Issue 3 Pg. 350-64 (Sep 2012) ISSN: 1365-2559 [Electronic] England
PMID22690749 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2012 Blackwell Publishing Ltd.
Chemical References
  • Biomarkers, Tumor
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factor Receptor-1
Topics
  • Biomarkers, Tumor (analysis)
  • Breast Neoplasms (metabolism, mortality, pathology)
  • Carcinoma (metabolism, pathology)
  • Disease-Free Survival
  • Female
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Neoplasm Grading
  • Neoplasm Invasiveness (pathology)
  • Neoplasm Staging
  • Neovascularization, Pathologic (metabolism, pathology)
  • Prognosis
  • Vascular Endothelial Growth Factor A (biosynthesis)
  • Vascular Endothelial Growth Factor Receptor-1 (biosynthesis)

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