Lmmunohistochemical detection of HIF-1α and CAIX in advanced head-and-neck cancer
Lmmunohistochemical detection of HIF-1α and CAIX in advanced head-and-neck cancer
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DOI：
10.1007/s00066-008-1813-7
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发表时间：
2008-08-01
影响因子：
3.1
通讯作者：
Bache, Matthias
中科院分区：
文献类型：
--
作者：
Kappler, Matthias;Taubert, Helge;Bache, Matthias
背景：肿瘤缺氧对接受放射治疗的癌症患者的预后有影响。缺氧诱导因子 1 α (HIF-1 α) 和碳酸酐酶同工酶 IX (CAIX) 等内源性标记物检测肿瘤内治疗相关缺氧水平的有效性存在争议。此外，这些缺氧标志物与肿瘤标志物或肿瘤氧合参数的关联对于理解不同因素之间的关系非常重要。 患者和方法：采用免疫组织化学方法评估34例接受放（化疗）治疗的晚期头颈癌患者的肿瘤组织切片中HIF-1α和CAIX的表达。研究了这两种标志物与肿瘤氧合参数、P53、OPN、VEGF、VHL、生存素和Ki67水平等分子因子以及临床参数的关系。结果：双变量分析显示HIF-1α表达与P53和OPN高表达、血清VEGF高水平以及VHL和Ki67低表达显着相关。 CAIX表达与pH值呈负相关，与T期呈正相关。然而，没有发现HIF-1α和CAIX表达之间存在相关性。在单变量 Cox 比例风险回归和 Kaplan-Meier 分析中，HIF-1 α 或 CAIX 的表达均未对临床结果产生显着影响。然而，在 Kaplan-Meier 分析中，这两个因素的组合显示，肿瘤内 HIF-1 α 或 CAIX 或两种标志物过表达的患者比肿瘤内两种因子低表达的患者平均早 2 年死亡（p < 0.05）。结论：HIF-1 α 和 CAIX 的表达与不同的肿瘤参数相关。只有结合 HIF-1 α 和 CAIX 表达才能显着预测患者的总生存期。
Background: Tumor hypoxia has an impact on the outcome of cancer patients treated with radiotherapy. The validity of endogenous markers such as hypoxia-inducible factor-1 alpha (HIF-1 alpha) and carbonic anhydrase isozyme IX (CAIX) to detect therapeutically relevant levels of hypoxia within tumors is controversially discussed. Furthermore, the association of these hypoxia markers with tumor markers or tumor oxygenation parameters is of importance for understanding the relationship between the different factors.Patients and Methods: Tumor tissue sections of 34 patients with advanced head-and-neck cancer treated with radio(chemo)therapy were assessed by immunohistochemistry for the expression of HIF-1 alpha and CAIX. The relationships of both markers with tumor oxygenation parameters, molecular factors like P53, OPN, VEGF, VHL, survivin, and Ki67 levels, and clinical parameters were studied.Results: Bivariate analysis showed a significant correlation of HIF-1 alpha expression with high P53 and high OPN expression, high serum VEGF levels, and low VHL and tow Ki67 expression. The CAIX expression was inversely correlated with pH value and directly correlated with T-stage. However, no correlation was found between HIF-1 alpha and CAIX expression. Neither in a univariate Cox proportional hazard regression nor in a Kaplan-Meier analysis did expression of HIF-1 alpha or CAIX have a significant impact on clinical outcome. However, in a Kaplan-Meier analysis, the combination of both factors showed that patients with intratumoral overexpression of either HIF-1 alpha or CAIX or both markers died on average 2 years earlier than patients whose tumors had Low expression of both factors (p < 0.05).Conclusion: Expression of HIF-1 alpha and CAIX was correlated with different tumor parameters. Only combined HIF-1 alpha and CAIX expression was significantly predictive of patients' overall survival.