Gibson-Corley Katherine N, Rogers Laura M, Goeken Adam, Dupuy Adam J, Meyerholz David K
Department of Pathology, University of Iowa, Iowa City, IA 52242, USA.
Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA 52242, USA.
Diseases. 2014 May 23;2(2):106-119. doi: 10.3390/diseases2020106.
Recently we described skin tumors driven by skin-specific expression of and here we define keratoacanthoma pathobiology in this mouse model. Similar to human keratoacanthoma development, we were able to segregate murine keratoacanthomas into three developmental phases: growth, maturation, and regression. These tumors had areas with cellular atypia, high mitotic rate, and minor local invasion in the growth phase, but with development they transitioned to maturation and regression phases with evidence of resolution. The early aggressive appearance could easily be misdiagnosed as a malignant change if the natural pathobiology was not well-defined in the model. To corroborate these findings in the model, we examined squamous skin tumors from another tumor study in aging mice, and these tumors followed a similar biological progression. Lastly, we were able to evaluate the utility of the model to assess immune cell infiltration (F4/80, B220 Granzyme B, CD3 cells, arginase-1) in the regression phase; however, because inflammation was present at all phases of development, a more comprehensive approach will be needed in future investigations. Our study of keratoacanthomas in selected murine models suggests that these squamous tumors can appear histologically aggressive during early development, but with time will enter a regression phase indicating a benign biology. Importantly, studies of squamous skin tumor models should be cautious in tumor diagnosis as the early growth distinction between malignant benign based solely on histopathology may not be easily discerned without longitudinal studies to confirm the tumor pathobiology.
最近我们描述了由[具体基因名称]的皮肤特异性表达驱动的皮肤肿瘤，在此我们定义了这种小鼠模型中的角化棘皮瘤病理生物学。与人类角化棘皮瘤的发展相似，我们能够将小鼠角化棘皮瘤分为三个发育阶段：生长、成熟和消退。这些肿瘤在生长阶段有细胞异型性、高有丝分裂率和轻微局部浸润的区域，但随着发育，它们过渡到成熟和消退阶段并有消退的迹象。如果在模型中没有很好地定义其自然病理生物学，早期的侵袭性表现很容易被误诊为恶性变化。为了在[具体基因名称]模型中证实这些发现，我们检查了另一项老年小鼠肿瘤研究中的鳞状皮肤肿瘤，这些肿瘤遵循类似的生物学进展。最后，我们能够评估该模型在评估消退阶段免疫细胞浸润（F4/80、B220、颗粒酶B、CD3细胞、精氨酸酶-1）方面的效用；然而，由于在发育的所有阶段都存在炎症，未来的研究将需要一种更全面的方法。我们在选定的小鼠模型中对角化棘皮瘤的研究表明，这些鳞状肿瘤在早期发育过程中在组织学上可能表现出侵袭性，但随着时间的推移会进入消退阶段，表明其生物学特性为良性。重要的是，在鳞状皮肤肿瘤模型的研究中，肿瘤诊断应谨慎，因为仅基于组织病理学很难轻易区分早期生长阶段的恶性与良性，而没有纵向研究来证实肿瘤的病理生物学。
