TY - JOUR
T1 - Co-expression of angiogenic markers and associations with prognosis in advanced epithelial ovarian cancer
T2 - A Gynecologic Oncology Group study
AU - Secord, Angeles Alvarez
AU - Darcy, Kathleen M.
AU - Hutson, Alan
AU - Lee, Paula S.
AU - Havrilesky, Laura J.
AU - Grace, Lisa A.
AU - Berchuck, Andrew
N1 - Funding Information:
This study was supported by the American Association of Obstetricians and Gynecologists Foundation and the National Cancer Institute grants to the Gynecologic Oncology Group (GOG) Administrative Office along with the GOG Tissue Bank (CA 27469) and the GOG Statistical Office (CA 37517). The following Gynecologic Oncology Group member institutions participated in this study: University of Alabama at Birmingham, Oregon Health Sciences University, Duke University Medical Center, Abington Memorial Hospital, University of Rochester Medical Center, Walter Reed Army Medical Center, Wayne State University, University of Minnesota Medical School, University of Southern California at Los Angeles, University of Mississippi Medical Center, Colorado Gynecologic Oncology Group P.C., University of California at Los Angeles, University of Washington, University of Pennsylvania Cancer Center, University of Miami School of Medicine, Milton S. Hershey Medical Center, Georgetown University Hospital, University of Cincinnati, University of North Carolina School of Medicine, University of Iowa Hospitals and Clinics, University of Texas Southwestern Medical Center at Dallas, Indiana University School of Medicine, Wake Forest University School of Medicine, Albany Medical College, University of California Medical Center at Irvine, Tufts-New England Medical Center, Rush-Presbyterian-St. Luke's Medical Center, University of Kentucky, Eastern Virginia Medical School, The Cleveland Clinic Foundation, Johns Hopkins Oncology Center, State University of New York at Stony Brook, Eastern Pennsylvania GYN/ONC Center, P.C., Southwestern Oncology Group, Washington University School of Medicine, Memorial Sloan-Kettering Cancer Center, Columbus Cancer Council, University of Massachusetts Medical School, Fox Chase Cancer Center, Medical University of South Carolina, Women's Cancer Center, University of Oklahoma, University of Virginia Health Sciences Center, University of Chicago, University of Arizona Health Science Center, Tacoma General Hospital, Eastern Collaborative Oncology Group, Thomas Jefferson University Hospital, Case Western Reserve University and Tampa Bay Cancer Consortium.
PY - 2007/7
Y1 - 2007/7
N2 - Objectives: The aim of this study was to explore the co-expression and prognostic relevance of thrombospondin-1 (THBS-1), basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF) and VEGF receptor 1 (VEGFR-1) in epithelial ovarian cancer (EOC). Methods: Frozen tumor specimens with defined p53 status were obtained from 67 patients with previously untreated advanced-stage EOC who participated in a Gynecologic Oncology Group specimen-banking protocol and a phase III treatment protocol. Relative expression of the angiogenic markers was quantified by immunoblot analysis and categorized at the median angiogenic marker/actin ratio. p-values are provided as an indication of confidence in the results and to prioritize further testing. Results: An association was observed between categorized VEGF and p53 overexpression (p = 0.022), and between VEGFR-1 and race (p = 0.027) or histologic subtype (p = 0.007). Unadjusted Cox regression analyses indicated that high compared with low THBS-1, but not VEGF or VEGFR-1, was associated with an increased risk of disease progression (hazard ratio [HR] = 2.19; 95% confidence interval [CI] = 1.29-3.71; p = 0.004) and death (HR = 1.93; 95% CI = 1.12-3.32; p = 0.018) whereas bFGF was associated with a reduced risk of disease progression (HR = 0.60; 95% CI = 0.36-0.99; p = 0.046) and death (HR = 0.54; 95% CI = 0.32-0.93; p = 0.026). After adjusting for prognostic factors including clinical characteristics and p53 overexpression, THBS-1 but not bFGF, VEGF or VEGFR-1 was associated with progression-free and overall survival. Conclusions: These data suggest that high THBS-1 is an independent predictor of worse progression-free and overall survival in women with advanced-stage EOC. A larger prospective study is warranted for validation of these findings.
AB - Objectives: The aim of this study was to explore the co-expression and prognostic relevance of thrombospondin-1 (THBS-1), basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF) and VEGF receptor 1 (VEGFR-1) in epithelial ovarian cancer (EOC). Methods: Frozen tumor specimens with defined p53 status were obtained from 67 patients with previously untreated advanced-stage EOC who participated in a Gynecologic Oncology Group specimen-banking protocol and a phase III treatment protocol. Relative expression of the angiogenic markers was quantified by immunoblot analysis and categorized at the median angiogenic marker/actin ratio. p-values are provided as an indication of confidence in the results and to prioritize further testing. Results: An association was observed between categorized VEGF and p53 overexpression (p = 0.022), and between VEGFR-1 and race (p = 0.027) or histologic subtype (p = 0.007). Unadjusted Cox regression analyses indicated that high compared with low THBS-1, but not VEGF or VEGFR-1, was associated with an increased risk of disease progression (hazard ratio [HR] = 2.19; 95% confidence interval [CI] = 1.29-3.71; p = 0.004) and death (HR = 1.93; 95% CI = 1.12-3.32; p = 0.018) whereas bFGF was associated with a reduced risk of disease progression (HR = 0.60; 95% CI = 0.36-0.99; p = 0.046) and death (HR = 0.54; 95% CI = 0.32-0.93; p = 0.026). After adjusting for prognostic factors including clinical characteristics and p53 overexpression, THBS-1 but not bFGF, VEGF or VEGFR-1 was associated with progression-free and overall survival. Conclusions: These data suggest that high THBS-1 is an independent predictor of worse progression-free and overall survival in women with advanced-stage EOC. A larger prospective study is warranted for validation of these findings.
KW - Angiogenesis
KW - Ovarian carcinoma
KW - THBS-1
KW - VEGF
KW - bFGF
KW - p53
UR - http://www.scopus.com/inward/record.url?scp=34250304711&partnerID=8YFLogxK
U2 - 10.1016/j.ygyno.2007.03.021
DO - 10.1016/j.ygyno.2007.03.021
M3 - Article
C2 - 17481705
AN - SCOPUS:34250304711
SN - 0090-8258
VL - 106
SP - 221
EP - 232
JO - Gynecologic Oncology
JF - Gynecologic Oncology
IS - 1
ER -