Prognostic significance of vascular endothelial growth factor and cyclooxygenase 2 expression in patients receiving preoperative chemoradiation for esophageal cancer.
OBJECTIVE
Both vascular endothelial growth factor and cyclooxygenase 2 overexpression have been associated with poor prognosis in a variety of human malignancies. In this study we assessed the effect of preoperative chemotherapy and radiation on expression levels of vascular endothelial growth factor and cyclooxygenase 2 in patients with esophageal cancer and determined whether these markers were associated with treatment response and overall survival.


METHODS
Expression levels of vascular endothelial growth factor and cyclooxygenase 2 were measured in a cohort of 46 patients with esophageal cancer receiving preoperative chemoradiation followed by surgical resection. Immunohistochemical stains were performed on both pretreatment biopsy specimens and posttreatment resection specimens for each patient. Differences in vascular endothelial growth factor and cyclooxygenase 2 expression before and after treatment were measured, and pretreatment expression levels were correlated with treatment response and overall survival.


RESULTS
We found that preoperative chemotherapy and radiation induced expression of cyclooxygenase 2 in stromal cells and induced vascular endothelial growth factor expression in both tumor and stromal cells. Pretreatment vascular endothelial growth factor expression did not correlate with treatment response, and cyclooxygenase 2 expression correlated with treatment response only in the subset of patients with squamous cell carcinoma. Although patients whose tumors expressed high levels of vascular endothelial growth factor and cyclooxygenase 2 tended to have shorter overall survival times, this trend did not reach statistical significance.


CONCLUSIONS
Neither vascular endothelial growth factor nor cyclooxygenase 2 are strong predictors of treatment response and survival in patients undergoing preoperative chemoradiation for esophageal cancer. This lack of prognostic significance might be explained by changes in the expression levels of these markers during treatment.
Kulke
Matthew H
MH
Department of Adult Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA. matthew_kulke@dfci.harvard.edu
Odze
Robert D
RD
Mueller
James D
JD
Wang
Helen
H
Redston
Mark
M
Bertagnolli
Monica M
MM
D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D017024:Chemotherapy, Adjuvant; D015331:Cohort Studies; D003131:Combined Modality Therapy; D051546:Cyclooxygenase 2; D004938:Esophageal Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D016629:Esophagectomy / Q000379:methods; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000032:analysis / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D011237:Predictive Value of Tests; D011300:Preoperative Care; D011336:Probability; D011379:Prognosis; D016016:Proportional Hazards Models; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis / Q000378:metabolism*; D018714:Radiotherapy, Adjuvant; D012189:Retrospective Studies; D018570:Risk Assessment; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis / Q000378:metabolism*
D014408:Biomarkers, Tumor; D007527:Isoenzymes; D008565:Membrane Proteins; D042461:Vascular Endothelial Growth Factor A; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases