Anaplastic thyroid carcinoma: vimentin segregates at the invasive front of tumors in a murine xenograft model.

Abstract

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.