Haustermans K, Hofland I, Van de Pavert L, Geboes K, Varia M, Raleigh J, Begg A C
Division of Experimental Therapy, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, The, Amsterdam, Netherlands.
Radiother Oncol. 2000 Jun;55(3):325-33. doi: 10.1016/s0167-8140(00)00206-1.
To assess diffusion limited hypoxia in human tumors using image analysis of vasculature and to compare it with the bioreductive marker pimonidazole as an independent method.
To set up the method, nine rectal adenocarcinomas and ten squamous cell carcinomas were analyzed. To validate the method, ten squamous cell carcinomas of the cervix were analyzed from patients who were injected with pimonidazole and biopsied approximately 24 h later. Sections of the rectal and esophageal tumors were stained for vasculature, while cervix tumor sections were double stained for vasculature and pimonidazole. Tumor areas were delineated on digitized images, and the proportion of tumor tissue greater than a fixed distance from the nearest blood vessel (called diffusion limited fraction, DLF) was then calculated. The proportion of tumor area stained for pimonidazole was also measured.
There was a wide variation between tumors in both the vascular-derived DLF and in the pimonidazole-stained fraction. Average DLFs varied between 1.5 and 92% for different tumors, with significant differences between them. The area stained by pimonidazole was significantly smaller than DLF for all tumors. The correlation between pimonidazole area and DLF was significant in three of seven tumors containing > or = 3 images. When images from all tumors (n=123) were analyzed together, the correlation was highly significant (r=0.47, P<0.0001).
The vascular derived DLF correlates significantly with pimonidazole staining, but there was large scatter. Both methods may underestimate perfusion limited hypoxia.
通过血管系统的图像分析评估人类肿瘤中的扩散受限性缺氧，并将其与生物还原标记物匹莫硝唑作为一种独立方法进行比较。
为建立该方法，分析了9例直肠腺癌和10例鳞状细胞癌。为验证该方法，对10例宫颈鳞状细胞癌患者进行了分析，这些患者注射了匹莫硝唑，并在约24小时后进行活检。直肠和食管肿瘤切片进行血管染色，而宫颈肿瘤切片进行血管和匹莫硝唑双重染色。在数字化图像上勾勒出肿瘤区域，然后计算距离最近血管大于固定距离的肿瘤组织比例（称为扩散受限分数，DLF）。还测量了匹莫硝唑染色的肿瘤面积比例。
血管源性DLF和匹莫硝唑染色分数在不同肿瘤之间存在很大差异。不同肿瘤的平均DLF在1.5%至92%之间变化，它们之间存在显著差异。所有肿瘤中匹莫硝唑染色的面积均明显小于DLF。在7例包含≥3张图像的肿瘤中，有3例匹莫硝唑染色面积与DLF之间的相关性显著。当对所有肿瘤（n = 123）的图像一起进行分析时，相关性非常显著（r = 0.47，P < 0.0001）。
血管源性DLF与匹莫硝唑染色显著相关，但存在较大离散度。两种方法都可能低估灌注受限性缺氧。
