TY - JOUR
T1 - Independent prognostic relevance of microvessel density in advanced epithelial ovarian cancer and associations between CD31, CD105, p53 status, and angiogenic marker expression
T2 - A Gynecologic Oncology Group study
AU - Rubatt, Jennifer M.
AU - Darcy, Kathleen M.
AU - Hutson, Alan
AU - Bean, Sarah M.
AU - Havrilesky, Laura J.
AU - Grace, Lisa A.
AU - Berchuck, Andrew
AU - Secord, Angeles Alvarez
N1 - Funding Information:
This study was supported by the American Association of Obstetricians and Gynecologists Foundation, Berlex Scholar Award in Basic Science, Gynecological Oncology Group Young Investigator Award, and National Cancer Institute grants to the Gynecologic Oncology Group (GOG) Administrative Office (CA 27469), the GOG Tissue Bank (CA 11479) and the GOG Statistical and Data Center (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 - 2009/3
Y1 - 2009/3
N2 - Objectives: The aims of this study were to examine prognostic significance of microvessel density (MVD) in previously-untreated, advanced epithelial ovarian cancer (EOC) and explore associations between MVD and factors that affect angiogenesis. Methods: MVD was determined by immunohistochemical expression of CD31 or CD105 in tumor sections from 106 women treated on GOG randomized phase III trials. Average MVD hotspots were quantified by light microscopy at high power (×400) and categorized as low (< upper quartile) or high (≥ upper quartile). Immunoblot expression of MASPIN, THBS-1, bFGF, VEGF, VEGFR-1 and p53 status (mutation and overexpression) was previously determined. Results: Of 106 evaluable cases, 25% exhibited high CD31-MVD (> 24.25 vessels/high power field [HPF]) or high CD105-MVD (> 19.25 vessels/HPF). After adjusting for age and stratifying by GOG performance status, stage, cell type, grade, debulking status and treatment regimen, high versus low CD105-MVD was associated with increased risk of disease progression (hazard ratio [HR] = 1.873; 95% confidence interval [CI]: 1.102-3.184; p = 0.020), but not death (HR = 1.125; 95% CI: 0.654-1.935; p = 0.670) whereas CD31-MVD was not associated with risk of disease progression (HR = 1.578; 95% CI = 0.918-2.711; p = 0.099) or death (HR = 1.678; 95% CI = 0.957-2.943; p = 0.071). CD31-MVD was correlated with CD105-MVD (p = 0.001) and MASPIN (p = 0.016). Neither CD31-MVD nor CD105-MVD was associated with p53 status, THBS-1, bFGF, VEGF or VEGFR-1. Conclusions: High MVD assessed using CD105, a marker of proliferating endothelial cells and neoangiogenesis, but not CD31 a pan-endothelial marker, appeared to be an independent prognostic factor for worse progression-free survival in women with advanced EOC after adjusting for prognostic clinical covariates.
AB - Objectives: The aims of this study were to examine prognostic significance of microvessel density (MVD) in previously-untreated, advanced epithelial ovarian cancer (EOC) and explore associations between MVD and factors that affect angiogenesis. Methods: MVD was determined by immunohistochemical expression of CD31 or CD105 in tumor sections from 106 women treated on GOG randomized phase III trials. Average MVD hotspots were quantified by light microscopy at high power (×400) and categorized as low (< upper quartile) or high (≥ upper quartile). Immunoblot expression of MASPIN, THBS-1, bFGF, VEGF, VEGFR-1 and p53 status (mutation and overexpression) was previously determined. Results: Of 106 evaluable cases, 25% exhibited high CD31-MVD (> 24.25 vessels/high power field [HPF]) or high CD105-MVD (> 19.25 vessels/HPF). After adjusting for age and stratifying by GOG performance status, stage, cell type, grade, debulking status and treatment regimen, high versus low CD105-MVD was associated with increased risk of disease progression (hazard ratio [HR] = 1.873; 95% confidence interval [CI]: 1.102-3.184; p = 0.020), but not death (HR = 1.125; 95% CI: 0.654-1.935; p = 0.670) whereas CD31-MVD was not associated with risk of disease progression (HR = 1.578; 95% CI = 0.918-2.711; p = 0.099) or death (HR = 1.678; 95% CI = 0.957-2.943; p = 0.071). CD31-MVD was correlated with CD105-MVD (p = 0.001) and MASPIN (p = 0.016). Neither CD31-MVD nor CD105-MVD was associated with p53 status, THBS-1, bFGF, VEGF or VEGFR-1. Conclusions: High MVD assessed using CD105, a marker of proliferating endothelial cells and neoangiogenesis, but not CD31 a pan-endothelial marker, appeared to be an independent prognostic factor for worse progression-free survival in women with advanced EOC after adjusting for prognostic clinical covariates.
KW - Angiogenesis
KW - CD105
KW - CD31
KW - Microvessel density
KW - Ovarian cancer
KW - Prognosis
UR - http://www.scopus.com/inward/record.url?scp=60449117723&partnerID=8YFLogxK
U2 - 10.1016/j.ygyno.2008.11.030
DO - 10.1016/j.ygyno.2008.11.030
M3 - Article
C2 - 19135712
AN - SCOPUS:60449117723
SN - 0090-8258
VL - 112
SP - 469
EP - 474
JO - Gynecologic Oncology
JF - Gynecologic Oncology
IS - 3
ER -