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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
Author(s) -
Dhakal Hari Prasad,
Naume Bjørn,
Synnestvedt Marit,
Borgen Elin,
Kaaresen Rolf,
Schlichting Ellen,
Wiedswang Gro,
Bassarova Assia,
Holm Ruth,
Giercksky KarlErik,
Nesland Jahn M
Publication year - 2012
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/j.1365-2559.2012.04223.x
Subject(s) - vascular endothelial growth factor , angiogenesis , breast cancer , breast carcinoma , medicine , kinase insert domain receptor , vascular endothelial growth factor c , pathology , vascular endothelial growth factor a , oncology , immunohistochemistry , cancer , vegf receptors
Dhakal H P, Naume B, Synnestvedt M, Borgen E, Kaaresen R, Schlichting E, Wiedswang G, Bassarova A, Holm R, Giercksky K‐E & Nesland J M
(2012) Histopathology 61, 350–364 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 Aims: 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.