TY - JOUR
T1 - Markers of angiogenesis in high-risk, early-stage cervical cancer
T2 - A Gynecologic Oncology Group study
AU - Randall, Leslie M.
AU - Monk, Bradley J.
AU - Darcy, Kathleen M.
AU - Tian, Chunqiao
AU - Burger, Robert A.
AU - Liao, Shu Yuan
AU - Peters, William A.
AU - Stock, Richard J.
AU - Fruehauf, John P.
N1 - Funding Information:
This study was supported by National Cancer Institute grants to the Gynecologic Oncology Group (GOG) and the GOG Tissue Bank (CA 27469), the GOG Statistical and Data Center (CA 37517), and Dr. Monk (K23 CA 087558). The following Gynecologic Oncology Group member institutions participated in the primary treatment studies: University of Alabama at Birmingham, Oregon Health Sciences University, Duke University Medical Center, Walter Reed Medical Center, Wayne State University, University of Southern California at Los Angeles, 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 Medical Center, Wake Forest University School of Medicine, University of California Medical Center at Irvine, Tufts-New England Medical Center, Rush University Medical Center, SUNY Downstate Medical Center, Eastern Virginia Medical School, Johns Hopkins Cancer Center, State University of New York at Stony Brook, Washington University School of Medicine, Cooper Hospital/University Medical Center, Columbus Cancer Council, M. D. Anderson Cancer Center, University of Massachusetts Medical School, Fox Chase Cancer Center, Women's Cancer Center, University of Oklahoma, University of Virginia Health Sciences Center, University of Chicago, University of Arizona and Case Western Reserve University.
PY - 2009/3
Y1 - 2009/3
N2 - Objectives: To determine whether markers of tumor angiogenesis were associated with progression-free survival (PFS) and overall survival (OS) in women with high-risk, early-stage cervical cancer treated on a phase III trial. Methods: One hundred seventy-three tumor specimens were analyzed by semi-quantitative immunohistochemical (IHC) staining for vascular endothelial growth factor (VEGF, pro-angiogenesis factor), thrombospondin-1 (TSP-1, anti-angiogenesis factor), CD31 (non-specific endothelial marker), and CD105 (tumor-specific endothelial marker). Tumoral histoscores (HS) were calculated for VEGF using the formula: [% cells positive × (intensity + 1)]. TSP-1 specimens were categorized as negative or positive. CD31 and CD105 microvessel density (MVD) "hotspots" were counted in three 20× high-power fields. Associations between angiogenesis markers and survival were evaluated. Results: TSP-1 expression was observed in 65% of cases while 66% expressed high VEGF (≥ 200), 34% exhibited high CD31 (CD31 ≥ 110) and 66% displayed high CD105 (CD105 ≥ 28). In univariate analyses CD31 MVD, but not tumor TSP-1, was associated with improved PFS (HR = 0.37; 95% CI = 0.18-0.76; p = 0.007) and OS (HR = 0.37; 95% CI = 0.17-0.79; p = 0.010). After adjusting for prognostic clinical covariates, high CD31 MVD, but not TSP-1, VEGF or CD105 MVD, was an independent prognostic factor for PFS (HR = 0.36; 95% CI = 0.17-0.75; p = 0.006) and OS (HR = 0.36; 95% CI = 0.17-0.79; p = 0.010). Conclusions: Tumor angiogenesis measured by CD31 MVD is an independent prognostic factor for both PFS and OS in high-risk, early-stage cervical cancer. We hypothesize that this finding may be explained by improved treatment response in well-vascularized, well-oxygenated tumors.
AB - Objectives: To determine whether markers of tumor angiogenesis were associated with progression-free survival (PFS) and overall survival (OS) in women with high-risk, early-stage cervical cancer treated on a phase III trial. Methods: One hundred seventy-three tumor specimens were analyzed by semi-quantitative immunohistochemical (IHC) staining for vascular endothelial growth factor (VEGF, pro-angiogenesis factor), thrombospondin-1 (TSP-1, anti-angiogenesis factor), CD31 (non-specific endothelial marker), and CD105 (tumor-specific endothelial marker). Tumoral histoscores (HS) were calculated for VEGF using the formula: [% cells positive × (intensity + 1)]. TSP-1 specimens were categorized as negative or positive. CD31 and CD105 microvessel density (MVD) "hotspots" were counted in three 20× high-power fields. Associations between angiogenesis markers and survival were evaluated. Results: TSP-1 expression was observed in 65% of cases while 66% expressed high VEGF (≥ 200), 34% exhibited high CD31 (CD31 ≥ 110) and 66% displayed high CD105 (CD105 ≥ 28). In univariate analyses CD31 MVD, but not tumor TSP-1, was associated with improved PFS (HR = 0.37; 95% CI = 0.18-0.76; p = 0.007) and OS (HR = 0.37; 95% CI = 0.17-0.79; p = 0.010). After adjusting for prognostic clinical covariates, high CD31 MVD, but not TSP-1, VEGF or CD105 MVD, was an independent prognostic factor for PFS (HR = 0.36; 95% CI = 0.17-0.75; p = 0.006) and OS (HR = 0.36; 95% CI = 0.17-0.79; p = 0.010). Conclusions: Tumor angiogenesis measured by CD31 MVD is an independent prognostic factor for both PFS and OS in high-risk, early-stage cervical cancer. We hypothesize that this finding may be explained by improved treatment response in well-vascularized, well-oxygenated tumors.
KW - Angiogenesis
KW - Angiogenic markers
KW - Cervical cancer
KW - GOG
UR - http://www.scopus.com/inward/record.url?scp=60449083456&partnerID=8YFLogxK
U2 - 10.1016/j.ygyno.2008.11.013
DO - 10.1016/j.ygyno.2008.11.013
M3 - Article
C2 - 19110305
AN - SCOPUS:60449083456
SN - 0090-8258
VL - 112
SP - 583
EP - 589
JO - Gynecologic Oncology
JF - Gynecologic Oncology
IS - 3
ER -