High levels of vascular endothelial growth factor and its receptors (VEGFR-1, VEGFR-2, neuropilin-1) are associated with worse outcome in breast cancer.
Vascular endothelial growth factor has been shown to be up-regulated in breast cancers. Vascular endothelial growth factor receptors, VEGFR-1 and VEGFR-2, are the principal mediators of its effects. Together with VEGFR-1 and VEGFR-2, neuropilin-1 may act as a coreceptor for vascular endothelial growth factor. Although vascular endothelial growth factor exerts important effects on endothelial cells, VEGFRs are likely present on tumor cells as well. We used AQUA to analyze tumor-specific expression of vascular endothelial growth factor, VEGFR-1, VEGFR-2, and neuropilin-1 on a large cohort of breast cancer tissue microarray. Two-fold redundant arrays were constructed from 642 cases of primary breast adenocarcinomas. Automated image analysis with AQUA (Automated Quantitative Analysis) was then performed to determine a quantitative expression score. Scores from redundant arrays were normalized and averaged. Kaplan-Meier survival analysis showed that high levels of vascular endothelial growth factor, VEGFR-1, VEGFR-2, and neuropilin-1 were all significantly associated with survival (Miller Siegmeund corrected P = .0020, .0160, and .0320, respectively). In addition, vascular endothelial growth factor and neuropilin-1 retained a significant association with survival independent of other standard prognostic factors. Vascular endothelial growth factor, VEGFR-1 and -2, and neuropilin-1 are expressed to varying degrees in primary breast cancers and have prognostic significance. Further study of the functional significance of this finding is warranted as well as the prognostic value of these biomarkers in other tumor microenvironment-specific compartments (eg, vessels).
Ghosh
Sriparna
S
Section of Medical Oncology, Yale Cancer Center, Yale University School of Medicine, New Haven, CT 06520, USA.
Sullivan
Catherine A W
CA
Zerkowski
Maciej P
MP
Molinaro
Annette M
AM
Rimm
David L
DL
Camp
Robert L
RL
Chung
Gina G
GG
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D018275:Carcinoma, Lobular / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D003237:Connecticut / Q000453:epidemiology; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007124:Immunoenzyme Techniques; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D039942:Neuropilin-1; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism*; D015996:Survival Rate; D046888:Tissue Array Analysis; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D055815:Young Adult
D014408:Biomarkers, Tumor; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D039942:Neuropilin-1; D040262:Receptors, Vascular Endothelial Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2