Department of Radiation Oncology, 341, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
Eur J Cancer. 2009 Nov;45(16):2906-14. doi: 10.1016/j.ejca.2009.07.012. Epub 2009 Aug 19.
Tumour hypoxia as driving force in tumour progression and treatment resistance has been well established. Assessment of oxygenation status of tumours may provide important prognostic information and improve selection of patients for treatment. In this study, a large homogenous group of 103 laryngeal carcinomas has been investigated in the presence of hypoxia by pimonidazole binding and the usefulness of Carbonic anhydrase IX (CA-IX) and vascular parameters as surrogate markers of hypoxia. These parameters are further related to clinical and biological characteristics. One hundred and three patients with T2-T4 larynx carcinoma were included. They were given the hypoxia marker pimonidazole intravenously (i.v.) 2h prior to taking a biopsy. Expression of all the parameters was examined by immunohistochemistry, excluding large necrotic areas. Among tumours a large variation in pimonidazole positivity (hypoxic fraction based on pimonidazole, HFpimo) (range 0-19%) and CA-IX expression (hypoxic fraction based on CA-IX staining, HFCA-IX) (range 0-34%) was observed. In 67% of the tumours, hypoxia involved 1% of the viable tumour area. HFpimo and HFCA-IX correlated significantly albeit weak (p=0.04). Both parameters showed weak inverse correlations with the relative vascular area (RVA) (p=0.01). HFpimo was further associated with histopathological grade, with poorly differentiated tumours being more hypoxic. The fraction of the tumour area positive for both pimonidazole and CA-IX correlated significantly with N stage. From these results, it was concluded that CA-IX and RVA have only limited value for measuring hypoxia and are not as robust as pimonidazole, probably due to the influence of other factors in the microenvironment. A combination of staining patterns of exogenous and endogenous markers might give important additive information about tumour biology and behaviour.
肿瘤缺氧作为肿瘤进展和治疗抵抗的驱动力已经得到充分证实。评估肿瘤的氧合状态可以提供重要的预后信息，并改善治疗患者的选择。在这项研究中，通过结合咪达唑仑结合，对 103 例喉癌进行了大规模同质组研究，以评估肿瘤缺氧情况，并研究碳酸酐酶 IX（CA-IX）和血管参数作为缺氧的替代标志物的有用性。这些参数进一步与临床和生物学特征相关。纳入 103 例 T2-T4 喉癌患者。在进行活检前 2 小时，患者静脉注射缺氧标志物咪达唑仑（i.v.）。通过免疫组织化学检查所有参数的表达，排除大的坏死区域。在肿瘤中，观察到咪达唑仑阳性（基于咪达唑仑的缺氧分数，HFpimo）（范围 0-19%）和 CA-IX 表达（基于 CA-IX 染色的缺氧分数，HFCA-IX）（范围 0-34%）的很大变化。在 67%的肿瘤中，缺氧涉及 1%的存活肿瘤区域。HFpimo 和 HFCA-IX 虽然较弱（p=0.04），但相关性显著。两个参数均与相对血管面积（RVA）呈弱负相关（p=0.01）。HFpimo 还与组织病理学分级相关，分化不良的肿瘤更为缺氧。同时对咪达唑仑和 CA-IX 呈阳性的肿瘤区域分数与 N 分期显著相关。根据这些结果，可以得出结论，CA-IX 和 RVA 对测量缺氧的价值有限，并且不如咪达唑仑可靠，这可能是由于微环境中其他因素的影响。外源性和内源性标志物的染色模式的组合可能会提供关于肿瘤生物学和行为的重要附加信息。
