Expression of carbonic anhydrase IX (CA IX), a hypoxia-related protein, rather than vascular-endothelial growth factor (VEGF), a pro-angiogenic factor, correlates with an extremely poor prognosis in esophageal and gastric adenocarcinomas
Expression of carbonic anhydrase IX (CA IX), a hypoxia-related protein, rather than vascular-endothelial growth factor (VEGF), a pro-angiogenic factor, correlates with an extremely poor prognosis in esophageal and gastric adenocarcinomas
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DOI：
10.1097/01.sla.0000201452.09591.f3
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发表时间：
2006-03-01
影响因子：
9
通讯作者：
Ectors, N
中科院分区：
文献类型：
--
作者：
Driessen, A;Landuyt, W;Ectors, N
目的：为了评估碳酸酐酶IX（CA IX）和血管内皮生长因子（VEGF）在食管和胃腺癌中的表达，并反过来与组织学亚型。摘要背景资料：肿瘤缺氧是治疗抵抗的重要因素。肿瘤中的低氧浓度刺激a.o.方法：采用免疫组化法检测39例食管癌、73例贲门癌和42例远端胃腺癌（UICC分型）石蜡包埋标本中CA IX和VEGF的表达。腺癌根据Lauren分类（肠型和弥漫型）进行亚型分析。统计分析：χ 2检验、Kaplan-Meier生存分析、log-rank检验和考克斯比例风险模型。然而，膀胱型腺癌表现出显着较高的表达CA IX以及VEGF比弥漫型肿瘤。VEGF表达与高微血管密度相关。尽管生存分析显示CA IX表达（P = 0.008）以及CA IX和VEGF的共表达（P = 0.008）与预后不良相关，只有CA IX表达是总生存率和无转移生存率的独立预后因素。CA IX和VEGF在肠型和弥漫型腺癌中表达的差异可能解释了这些肿瘤不同的临床行为。肿瘤中CA IX表达而不是VEGF阳性，使得能够鉴定亚群，其特征在于更具侵略性的行为和较差的预后。
Objective: To evaluate the expression of carbonic anhydrase IX (CA IX) and vascular-endothelial growth factor (VEGF) in esophageal and gastric adenocarcinomas and in turn with the histologic subtype.Summary Background Data: Tumor hypoxia is an important factor in therapy resistance. A low oxygen concentration in tumors stimulates a.o. the expression of CA IX, a marker of hypoxia, and VEGF, a pro-angiogenic factor.Methods: We evaluated the immunohistochemical expression of CA IX and VEGF on paraffin-embedded material of 154 resection specimens: 39 esophageal, 73 cardiac, and 42 distal gastric adenocarcinomas (UICC classification). The adenocarcinomas were subtyped according to the Lauren classification (intestinal- and diffuse-type). Statistical Analysis: chi(2) test, Kaplan-Meier survival analysis, log-rank test, and Cox proportional hazards model.Results: CA IX and VEGF expression were independent of the localization of the tumor. However, intestinal-type adenocarcinomas showed a significantly higher expression of CA IX as well as VEGF than diffuse-type tumors. VEGF expression was associated with a high microvessel density. Although survival analysis showed that CA IX expression (P = 0.008) as well as the coexpression of CA IX and VEGF (P = 0.008) correlate with a poor outcome, only CA IX expression is an independent prognostic factor for overall survival and metastasis-free survival.Conclusion: The difference in expression of CA IX and VEGF between intestinal- and diffuse-type adenocarcinomas may possibly explain the different clinical behavior of these tumors. CA IX expression, rather than VEGF positivity in tumors, enables the identification of a subpopulation, characterized by a more aggressive behavior and a poorer prognosis.