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首页> 外文期刊>British Journal of Cancer >Analysis of the intra- and intertumoral heterogeneity of hypoxia in pancreatic cancer patients receiving the nitroimidazole tracer pimonidazole
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Analysis of the intra- and intertumoral heterogeneity of hypoxia in pancreatic cancer patients receiving the nitroimidazole tracer pimonidazole

机译：硝基咪唑示踪剂吡莫尼唑对胰腺癌患者缺氧的瘤内和瘤间异质性分析

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Background: Hypoxia is thought to be an adverse feature of pancreatic cancer, but direct measurement in patients is technically challenging. To address this, we characterised the intra/interpatient heterogeneity of hypoxia in surgical specimens from patients who received the 2-nitroimidazole tracer pimonidazole pre-operatively. Methods: Pimondazole was given intravenously 16–20?h before pancreatectomy, and the extent and intratumoral heterogeneity of hypoxia determined by image analysis applied to multiple tissue blocks stained by immunohistochemistry. Intra/interpatient heterogeneity was estimated by variance component analysis. Results: Pimonidazole staining was analysed in 10 tumours. The extent of labelling varied amongst patients (0–26%), with a broader range of hypoxia in the epithelial (1–39%) compared with the stromal (1–13%) compartments. Variance component analysis demonstrated greater inter- than intrapatient variability of hypoxia, and that multiple (4–5) tumour sections are required to provide a consistent evaluation of its extent in individual tumours. Conclusions: There is significant intra- and intertumoral heterogeneity of hypoxia in pancreatic cancers, and these do not appear to be generally more hypoxic than other cancer types. This study establishes the feasibility to assess hypoxia in pancreatic cancer patients using pimonidazole, but questions the reliability of measurements made using a single tissue section.
机译：背景：低氧被认为是胰腺癌的不利特征，但是直接测量患者的技术难度。为了解决这个问题，我们从术前接受2-硝基咪唑示踪剂吡莫尼唑的患者的外科手术标本中表征了患者内/患者间低氧的异质性。方法：在胰腺切除术前16–20？h静脉给予吡莫达唑，并通过图像分析确定的低氧程度和瘤内异质性应用于免疫组织化学染色的多个组织块。通过方差成分分析来估计患者内/患者间的异质性。结果：分析了10个肿瘤中的吡莫尼唑染色。患者之间的标记程度各不相同（0–26％），与间质（1–13％）隔室相比，上皮缺氧的范围更广（1-39％）。方差成分分析显示，患者之间的缺氧变异性大于患者内部变异性，并且需要多个（4-5）个肿瘤切片才能对其在单个肿瘤中的程度提供一致的评估。结论：在胰腺癌中，缺氧存在明显的肿瘤内和肿瘤间异质性，而且这些缺氧似乎并不比其他类型的癌症更具缺氧性。这项研究建立了使用吡莫尼唑评估胰腺癌患者缺氧的可行性，但对使用单个组织切片进行测量的可靠性提出了质疑。

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