Institute of Science of Food Production, C.N.R. Unit of Lecce, ISPA-CNR, 73100, Lecce, Italy.
Department of Experimental Medicine, University of Salento, 73100, Lecce, Italy.
Histochem Cell Biol. 2024 Nov 18;163(1):6. doi: 10.1007/s00418-024-02329-2.
Anaplastic thyroid carcinoma (ATC) ranks among the most lethal human cancers. Increased migratory and invasive capabilities are critical in malignancy and are often secondary to epithelial-mesenchymal transition (EMT). However, it is not clear whether the invasive behavior of ATC is associated with the presence of EMT. In this study, we used a murine xenograft model (4-week-old male BALB/c NU/NU mice) with the human anaplastic cell line, FRO. We adopted an automated, eye-independent method to reconstruct the total/subtotal area of the tumors. To probe EMT, we evaluated the immunostaining of mesenchymal/epithelial markers at the front and center of the tumors. The transplanted cells invariably gave rise to tumor masses that histologically closely replicated patient tumors. The staining with hematoxylin-eosin and immunostaining with cytokeratin 18, an epithelial marker, were similar. However, the immunostaining of cytokeratin 18 versus vimentin, a mesenchymal marker, were strikingly dissimilar, since vimentin showed a staining concentrated at the front, rapidly declining towards the center of the tumor. The overlay, after color conversion, of cytokeratin and vimentin staining showed maximal coincidence at the front, which was rapidly lost towards the center. The results show EMT signs at the front of the ATC, which are probably at the basis of its tremendous invasiveness. Moreover, methodologically, an automated "eye-independent" acquisition of the total/subtotal area of the tumors drove the selection of second, high-magnification, automated field acquisition. Future studies may extend these results along the perspective of a personalized diagnostic procedure.
间变性甲状腺癌(ATC)是人类最致命的癌症之一。增加迁移和侵袭能力在恶性肿瘤中至关重要,通常继发于上皮-间充质转化(EMT)。然而,目前尚不清楚 ATC 的侵袭行为是否与 EMT 的存在有关。在这项研究中,我们使用了一种带有人类间变性细胞系 FRO 的小鼠异种移植模型(4 周龄雄性 BALB/c NU/NU 小鼠)。我们采用了一种自动的、不依赖于眼睛的方法来重建肿瘤的总/全面积。为了探究 EMT,我们评估了肿瘤前缘和中心的间充质/上皮标志物的免疫染色。移植细胞总是产生与患者肿瘤在组织学上非常相似的肿瘤团块。苏木精-伊红染色和上皮标志物角蛋白 18 的免疫染色相似。然而,角蛋白 18 与间充质标志物波形蛋白的免疫染色截然不同,因为波形蛋白在前缘集中染色,迅速向肿瘤中心下降。角蛋白和波形蛋白染色的叠加,经过颜色转换后,在前缘最大程度地吻合,然后迅速向中心丢失。结果显示 ATC 前缘存在 EMT 迹象,这可能是其巨大侵袭性的基础。此外,从方法学上讲,肿瘤总/全面积的自动“不依赖于眼睛”获取驱动了第二高倍自动场获取的选择。未来的研究可能会沿着个性化诊断程序的角度扩展这些结果。