VEGF and Ki-67 Expression in Colorectal Cancer: The Long-Term Impact on Recurrence and Mortality

pedro miguel dias dos Santos
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Abstract

Objectives: Colorectal cancer is the most frequent and mortal cancer in Portugal. Both angiogenesis and cellular proliferation are core mechanisms to tumoral progression, with VEGF (Vascular Endothelial Growth Factor) and Ki-67, respec-tively, being widely known markers of those two processes. The purposes of this study are to comprehend VEGF and Ki-67’s impact on colorectal cancer prognosis which include assessing its expression in primary colorectal cancer of patients who underwent surgery, establishing associations between the expression of VEGF and Ki-67 and discovering hypothetical associations between these biomarkers and clinicopathological aspects, relapse, and mortality of patients. Methods: A retrospective study was conducted in our hospital by including 512 patients submitted to surgery, from 2005 to 2010, with a post-operatory diagnosis of colorectal adenocarcinoma. The evaluation of expression of VEGF and Ki-67 in the obtained tissue was made through immunohistochemistry technique. The statistical analysis resourced to association tests and survival analysis. Results: VEGF-A showed association with the variable gender (p-value of 0.016), with its expression being more frequent in men. VEGF-C expression is more common in colon than in rectum (p- value of 0.042). VEGF-C is significantly associated with Ki-67 (p-value of 0.036), with 69.7% of cases where both are positive. All markers are significantly associated with the grade of differentiation, with the VEGF family generally more present in well or moderately differentiated tumours and Ki-67 in the poorly differentiated. While the survival time was generally lower in the presence of any marker or combination, no significant differences were found among the survival analysis. Conclusion: VEGF-A, VEGF-C and Ki-67 expression did not show impact on the prognosis of this sample of patients. There was no significant association with a poorer overall survival or a reduced disease-free survival.
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结直肠癌中VEGF和Ki-67的表达:对复发和死亡率的长期影响
目的:结直肠癌是葡萄牙最常见和最致命的癌症。血管生成和细胞增殖都是肿瘤进展的核心机制,血管内皮生长因子(VEGF)和Ki-67分别是众所周知的这两个过程的标志物。本研究的目的是了解VEGF和Ki-67对结直肠癌预后的影响,包括评估其在接受手术的原发性结直肠癌患者中的表达,建立VEGF和Ki-67表达之间的关联,并发现这些生物标志物与患者临床病理、复发和死亡率之间的假设关联。方法:回顾性分析我院2005 ~ 2010年收治的512例术后诊断为结直肠腺癌的手术患者。采用免疫组化技术检测所得组织中VEGF和Ki-67的表达。统计分析以关联试验和生存分析为主。结果:VEGF-A与可变性别相关(p值为0.016),且在男性中表达较多。VEGF-C在结肠中的表达高于直肠(p值为0.042)。VEGF-C与Ki-67显著相关(p值为0.036),两者均呈阳性的病例占69.7%。所有标志物均与分化程度显著相关,VEGF家族通常更多地存在于分化良好或中度的肿瘤中,Ki-67则存在于分化较差的肿瘤中。虽然存在任何标记或组合的生存时间通常较低,但在生存分析中没有发现显着差异。结论:VEGF-A、VEGF-C、Ki-67的表达对本组患者的预后无影响。与较差的总生存期或减少的无病生存期没有显著关联。
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