Kulke Matthew H, Odze Robert D, Mueller James D, Wang Helen, Redston Mark, Bertagnolli Monica M
Department of Adult Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
J Thorac Cardiovasc Surg. 2004 Jun;127(6):1579-86. doi: 10.1016/j.jtcvs.2003.12.034.
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.
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.
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.
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.
血管内皮生长因子（VEGF）和环氧合酶2（COX-2）的过表达均与多种人类恶性肿瘤的不良预后相关。在本研究中，我们评估了术前化疗和放疗对食管癌患者VEGF和COX-2表达水平的影响，并确定这些标志物是否与治疗反应和总生存期相关。
对46例接受术前放化疗后行手术切除的食管癌患者进行队列研究，检测其VEGF和COX-2的表达水平。对每位患者的治疗前活检标本和治疗后切除标本均进行免疫组织化学染色。测量治疗前后VEGF和COX-2表达的差异，并将治疗前表达水平与治疗反应和总生存期进行关联分析。
我们发现术前化疗和放疗可诱导基质细胞中COX-2的表达，并诱导肿瘤细胞和基质细胞中VEGF的表达。治疗前VEGF表达与治疗反应无关，COX-2表达仅在鳞状细胞癌患者亚组中与治疗反应相关。尽管肿瘤高表达VEGF和COX-2的患者总生存时间往往较短，但这一趋势未达到统计学意义。
对于接受术前放化疗的食管癌患者，VEGF和COX-2均不是治疗反应和生存的有力预测指标。这些标志物缺乏预后意义可能是由于治疗期间其表达水平发生了变化。
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