Abstract | 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 positivex(intensity+1)]. TSP-1 specimens were categorized as negative or positive. CD31 and CD105 microvessel density (MVD) "hotspots" were counted in three 20x 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 (>or=200), 34% exhibited high CD31 (CD31>or=110) and 66% displayed high CD105 (CD105>or=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.
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Authors | Leslie M Randall, Bradley J Monk, Kathleen M Darcy, Chunqiao Tian, Robert A Burger, Shu-Yuan Liao, William A Peters, Richard J Stock, John P Fruehauf |
Journal | Gynecologic oncology
(Gynecol Oncol)
Vol. 112
Issue 3
Pg. 583-9
(Mar 2009)
ISSN: 1095-6859 [Electronic] United States |
PMID | 19110305
(Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Research Support, N.I.H., Extramural)
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Chemical References |
- Antigens, CD
- Biomarkers, Tumor
- ENG protein, human
- Endoglin
- Platelet Endothelial Cell Adhesion Molecule-1
- Receptors, Cell Surface
- Thrombospondin 1
- Vascular Endothelial Growth Factor A
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Topics |
- Adult
- Aged
- Antigens, CD
(metabolism)
- Biomarkers, Tumor
(metabolism)
- Cohort Studies
- Combined Modality Therapy
- Disease-Free Survival
- Endoglin
- Female
- Humans
- Immunohistochemistry
- Middle Aged
- Neoplasm Staging
- Neovascularization, Pathologic
(metabolism, pathology)
- Platelet Endothelial Cell Adhesion Molecule-1
(metabolism)
- Receptors, Cell Surface
(metabolism)
- Risk Factors
- Thrombospondin 1
(metabolism)
- Uterine Cervical Neoplasms
(blood supply, drug therapy, metabolism, radiotherapy)
- Vascular Endothelial Growth Factor A
(metabolism)
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