Vascular endothelial growth factor, CD68, and epidermal growth factor receptor expression and survival in patients with stage II and stage III colon carcinoma - A role for the host response in prognosis
Vascular endothelial growth factor, CD68, and epidermal growth factor receptor expression and survival in patients with stage II and stage III colon carcinoma - A role for the host response in prognosis
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DOI：
10.1002/cncr.11152
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发表时间：
2003-02-15
期刊：
影响因子：
6.2
通讯作者：
Sahasrabudhe, DM
中科院分区：
文献类型：
--
作者：
Khorana, AA;Ryan, CK;Sahasrabudhe, DM
背景。阐明结肠癌具有预后意义的新治疗靶点对于改善预后至关重要。在当前的研究中，作者检查了原发性结肠癌病例中表皮生长因子受体（EGFR）和血管内皮生长因子（VEGF）的表达以及肿瘤相关巨噬细胞（TAM）/间质中的VEGF的表达，及其与生存的相关性。方法。作者确定了 1990 年至 1995 年间在罗彻斯特大学就诊的 131 名连续美国癌症联合委员会 II 期和 III 期结肠癌患者。通过免疫组织化学检查石蜡包埋的原发性结肠肿瘤中 VEGF、EGFR 和 CD68 的表达，并根据染色细胞的百分比进行分级。使用多变量 Cox 比例风险模型对数据进行分析。结果。未发现肿瘤中的 VEGF 表达与生存显着相关。然而，42% 的患者在 TAM/基质中表达 VEGF。该组的中位生存期为 9.7 年，而 VEGF 阴性（TAM/基质）组的中位生存期为 4.3 年（风险比为 0.57，95% 置信区间 [95% CII，0.34-0.95；P = 0.03）。尽管在多变量分析中发现单独的 TAM 浸润并不显着，但 CD68 和 VEGF（TAM/基质）的存在预示着生存率的提高（风险比为 0.48，95% Cl，0.28-0.83；P = 0.006）。发现高级别 EGFR 表达（大于或等于 2 级）与生存恶化的趋势相关。结论。与表达 VEGF 的 TAM 相关的中位生存期增加超过两倍，表明该细胞亚群在宿主对结肠癌的反应中发挥着迄今为止未知的作用，需要进一步研究。 EGFR 过度表达可能与生存恶化相关，这为抗 EGFR 药物作为辅助治疗的试验提供了理论依据。
BACKGROUND. The elucidation of new therapeutic targets of prognostic significance in colon carcinoma is necessary to improve outcomes. In the current study, the authors examined the expression of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) in primary colon carcinoma cases and VEGF in tumor-associated macrophages (TAM)/stroma, and their correlation with survival.METHODS. The authors identified 131 consecutive American Joint Committee on Cancer Stage II and Stage III colon carcinoma patients seen at the University of Rochester between 1990-1995. Expression of VEGF, EGFR, and CD68 were examined by immunohistochemistry in paraffin-embedded primary colon tumors and graded as the percentage of cells stained. Data were analyzed using a multivariate Cox proportional hazards model.RESULTS. VEGF expression in tumor was not found to be significantly associated with survival. However, 42% of the patients expressed VEGF in TAM/stroma. The median survival in this group was 9.7 years versus 4.3 years in the VEGF-negative (TAM/stroma) group (hazards ratio of 0.57, 95% confidence interval [95% CII, 0.34-0.95; P = 0.03). Although TAM infiltration alone was not found to be significant in multivariate analysis, the presence of both CD68 and VEGF (TAM/stroma) was predictive of improved survival (hazards ratio of 0.48, 95% Cl, 0.28-0.83; P = 0.006). High grades of EGFR expression (greater than or equal to Grade 2) were found to be associated with a trend toward worsened survival.CONCLUSIONS. The greater than twofold increase in median survival associated with VEGF-expressing TAM suggests a hitherto unknown role for this subset of cells in the host response to colon carcinoma and requires further investigation. Overexpression of EGFR may be associated with worsened survival, providing a rationale for trials of anti-EGFR agents as adjuvant therapy.