Carbonic anhydrase IX expression, a novel surrogate marker of tumor hypoxia, is associated with a poor prognosis in non-small-cell lung cancer
Carbonic anhydrase IX expression, a novel surrogate marker of tumor hypoxia, is associated with a poor prognosis in non-small-cell lung cancer
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DOI：
10.1200/jco.2003.11.132
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发表时间：
2003-02-01
影响因子：
45.3
通讯作者：
O'Byrne, KJ
中科院分区：
文献类型：
--
作者：
Swinson, DEB;Jones, JL;O'Byrne, KJ
目的：评价碳酸酐酶（CA）IX作为缺氧替代标志物的作用，并探讨非小细胞肺癌（NSCLC）中不同表达模式的预后意义。方法：采用标准免疫组织化学技术研究175例切除的非小细胞肺癌肿瘤中CA IX的表达。CA IX的表达通过蛋白质印迹法在常氧和低氧条件下生长的A549细胞系中测定。结果：81.8%的患者检测到CA IX免疫染色。CA IX在细胞膜（m）（P = .005）、细胞质（c）（P = .018）和间质（P < .001）的表达与肿瘤坏死（TN）的程度相关。从血管内皮到肿瘤细胞阳性开始的平均距离为90 μ m，相当于5.77 mmHg的氧分压。表达mCA IX的单个肿瘤细胞或肿瘤细胞簇与血管的距离大于不表达mCA IX的肿瘤细胞或肿瘤细胞簇与血管的距离（P <0.001）。A549细胞16小时的低氧暴露增强了细胞核和胞质提取物中的CA IX表达。核周CA IX（P = 0.035）与预后不良相关。在多变量分析中，pCA IX（P = 0.004），阶段（P = 0.001），血小板计数（P = 0.011），性别（P = 0.027），和TN（P = 0.035）是独立的预后不良factors.Conclusion：这些结果增加了重量的论点，mCA IX是肿瘤细胞缺氧的标志物。接近微血管的CA IX染色的缺乏表明这些血管是功能活性的。pCA IX表达代表侵袭性表型。(C)2003年，美国临床肿瘤学会。
Purpose: To evaluate carbonic anhydrase (CA) IX as a surrogate marker of hypoxia and investigate the prognostic significance of different patterns of expression in non-small-cell lung cancer (NSCLC).Methods: Standard immunohistochemical techniques were used to study CA IX expression in 175 resected NSCLC tumors. CA IX expression was determined by Western blotting in A549 cell lines grown under normoxic and hypoxic conditions. Measurements from microvessels to CA IX positivity were obtained.Results: CA IX immunostaining was detected in 81.8% of patients. Membranous (m) (P = .005), cytoplasmic (c) (P = .018), and stromal (P < .001) CA IX expression correlated with the extent of tumor necrosis (TN). The mean distance from vascular endothelium to the start of tumor cell positivity was 90 mum, which equates to an oxygen pressure of 5.77 mmHg. The distance to blood vessels from individual tumor cells or tumor cell clusters was greater if they expressed mCA IX than if they did not (P < .001). Hypoxic exposure of A549 cells for 16 hours enhanced CA IX expression in the nuclear and cytosolic extracts. Perinuclear (p) CA IX (P = .035) was associated with a poor prognosis. In multivariate analysis, pCA IX (P = .004), stage (P = .001), platelet count (P = .011), sex (P = .027), and TN (P = .035) were independent poor prognostic factors.Conclusion: These results add weight to the contention that mCA IX is a marker of tumor cell hypoxia. The absence of CA IX staining close to microvessels suggests that these vessels are functionally active. pCA IX expression is representative of an aggressive phenotype. (C) 2003 by American Society of Clinical Oncology.