Department of Oncology, Livestrong Cancer Institutes, Dell Medical School, The University of Texas at Austin, Health Learning Building, Austin, Texas, USA.
Department of Translational Medical Sciences, University of Campania L. Vanvitelli, Naples, Italy,
Kidney Blood Press Res. 2020;45(3):368-377. doi: 10.1159/000507581. Epub 2020 May 20.
BACKGROUND/AIMS: Basal cell carcinoma (BCC) is a frequent type of nonmelanoma skin cancer, which shows a greater prevalence in kidney-transplanted (KT) patients than in the general population. The study of this tumor in KT patients may allow us to understand the influence of the tumor inflammatory microenvironment on cancer behavior, and to design new image analysis methods to determine prognosis and apply personalized medicine. The major hypothesis of the present work is that antirejection drugs, by modifying the B-cell/T-cell balance, induce measurable differences in tumoral cell microarchitecture and in the inflammatory microenvironment in KT patients compared to nontransplanted controls.
In this retrospective study in an Italian cohort including 15 KT patients and 15 control subjects from the general population who developed BCC, we analyzed tissue microarchitecture and inflammatory infiltrates of BCC using state-of-the-art nonlinear image analysis techniques such as fractal dimension and sample entropy of internuclear distances.
KT patients showed a nonsignificant trend to a greater number of nuclei in the basal cell layer compared to non-KT controls and subtle changes in the intact skin compared to controls. Similarly, the number of mitoses per unit length was almost doubled in the patients with KT compared to controls. However, when the number of mitotic cells was normalized by the total number of cells in the basal layer (mitotic index), these differences were not significant, although a clear trend was still present. Finally, KT patients showed a nonsignificant trend to an increased -density of inflammatory cells close to the tumoral cell layer. When considering the intact skin, this difference was significant, with a 70% increase in the density of inflammatory cells.
Data comparing the microarchitecture of BCC in normal subjects and KT patients are scanty, and the present study is the first to use nonlinear image analysis techniques to this aim. The observed differences underscore the relevance of T-cell suppression in cancer behavior. These data suggest that BCC develops in treated patients with specific biological characteristics which should be further analyzed in terms of therapeutic response.
背景/目的：基底细胞癌（BCC）是一种常见的非黑色素瘤皮肤癌，在肾移植（KT）患者中的发病率高于普通人群。研究这种肿瘤在 KT 患者中的表现，可能有助于我们了解肿瘤炎症微环境对癌症行为的影响，并设计新的图像分析方法来确定预后和应用个体化医学。本研究的主要假设是，抗排斥药物通过改变 B 细胞/T 细胞平衡，在 KT 患者与非移植对照组之间引起肿瘤细胞微结构和炎症微环境的可测量差异。
在这项回顾性研究中，我们纳入了意大利队列中的 15 名 KT 患者和 15 名来自普通人群的 BCC 对照组，使用最新的非线性图像分析技术，如分形维数和核间距离的样本熵，分析 BCC 的组织微结构和炎症浸润。
与非 KT 对照组相比，KT 患者的基底细胞层中的细胞核数量呈现出无统计学意义的增加趋势，与对照组相比，正常皮肤也有细微的变化。同样，与对照组相比，KT 患者的单位长度有丝分裂细胞数几乎增加了一倍。然而，当将有丝分裂细胞数除以基底细胞层中的总细胞数（有丝分裂指数）时，这些差异并不显著，尽管仍然存在明显的趋势。最后，KT 患者的肿瘤细胞层附近的炎症细胞密度呈现出无统计学意义的增加趋势。当考虑正常皮肤时，这种差异是显著的，炎症细胞的密度增加了 70%。
比较正常人和 KT 患者 BCC 微结构的数据很少，本研究首次使用非线性图像分析技术来达到这一目的。观察到的差异强调了 T 细胞抑制在癌症行为中的重要性。这些数据表明，BCC 在接受治疗的患者中发展，具有特定的生物学特征，应进一步分析其治疗反应。
