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.
OBJECTIVE
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.


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.
Department of Pathology, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, Norway. hari.prasad.dhakal@oslo-universitetssykehus.no
Hari Prasad
HP
Dhakal
Bjørn
B
Naume
Marit
M
Synnestvedt
Elin
E
Borgen
Rolf
R
Kaaresen
Ellen
E
Schlichting
Gro
G
Wiedswang
Assia
A
Bassarova
Ruth
R
Holm
Karl-Erik
KE
Giercksky
Jahn M
JM
Nesland
D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000096:biosynthesis*
D014408:Biomarkers, Tumor; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1