Ljungkvist Anna S E, Bussink Johan, Rijken Paulus F J W, Kaanders Johannes H A M, van der Kogel Albert J, Denekamp Juliana
Department of Radiation Oncology, University Medical Center Nijmegen, PO Box 9101, NL-6500 HB Nijmegen, The Netherlands.
Int J Radiat Oncol Biol Phys. 2002 Sep 1;54(1):215-28. doi: 10.1016/s0360-3016(02)02938-3.
To quantify the physiologic status of human tumor cells in relation to the tumor vasculature.
Fourteen tumors of 11 first-generation xenograft lines of human head-and-neck squamous cell carcinoma were injected with the hypoxic cell marker pimonidazole, the proliferation marker BrdUrd, and the perfusion marker Hoechst 33342. Consecutive tissue sections were processed with immunohistochemical methods and analyzed with image-analysis techniques.
Three different hypoxic patterns were found: patchy, ribbon-like, and mixed. An image-analysis method was developed to quantify these, and an elongation index (length/width) was calculated for hypoxia. The mean elongation indices ranged from 2.0 to 28.3 and showed a good correlation with the visual scoring of hypoxic patterns. Comparative analysis of hypoxic and proliferating cells in zones around the tumor vasculature showed the presence of both hypoxic and proliferating cells in all zones up to 250 microm from the vessels. The largest coexistence of hypoxic and proliferating cells seemed to occur at 50-100 microm from the vessels.
The three hypoxic patterns could be quantified by an elongation index, which is an additional parameter that allows distinction of tumors with similar fractions of hypoxic cells. The analysis of hypoxic and proliferating cells as a function of distance from the tumor vasculature indicates that proliferation does occur also at low oxygen tensions.
量化人类肿瘤细胞相对于肿瘤脉管系统的生理状态。
对头颈部鳞状细胞癌的11个第一代异种移植瘤系的14个肿瘤注射缺氧细胞标记物匹莫硝唑、增殖标记物溴脱氧尿苷和灌注标记物 Hoechst 33342。连续组织切片采用免疫组织化学方法处理，并运用图像分析技术进行分析。
发现三种不同的缺氧模式：斑片状、带状和混合型。开发了一种图像分析方法对这些模式进行量化，并计算缺氧的伸长指数（长度/宽度）。平均伸长指数范围为2.0至28.3，与缺氧模式的视觉评分具有良好的相关性。对肿瘤脉管系统周围区域的缺氧细胞和增殖细胞进行比较分析，结果显示在距血管250微米范围内的所有区域均存在缺氧细胞和增殖细胞。缺氧细胞和增殖细胞的最大共存似乎发生在距血管50 - 100微米处。
三种缺氧模式可通过伸长指数进行量化，这是一个额外的参数，可用于区分缺氧细胞比例相似的肿瘤。对缺氧细胞和增殖细胞作为距肿瘤脉管系统距离的函数进行分析表明，在低氧张力下也确实会发生增殖。
