Fig. 2. Human and murine OSCC lesions. Left panel: Immunohistochemical analysis of a well-differentiated SCC of the human tongue stained for α3 integrin (A,B) and uPAR (C,D). Magnification 4X (A,C), 20X (B,D). Courtesy of Dr. Mark Lingen, Univ. of Chicago. Right panel: Orthotopic murine model of SCC of the oral tongue. Mice were injected in the anterior tongue with wild type SCC25 cells, pooled clones of uPAR-knockdown (SCC25-uPAR-KD), or pooled clones of uPAR-overexpressing (SCC25-uPAR/f) cells. Lesions produced by wild type SCC25 cells at 9 weeks appear multicentric with focal keratin formation at low power [2A]. Lesions are well-circumscribed and cuffed by inflammatory cells. At higher magnification, high vascularity and myxoid change is present in the adjacent stroma [2D]. In tumors formed by SCC25-uPAR-KD cells, low power evaluation demonstrates a fairly well-circumscribed tumor [2B]. Higher power examination [2E] reveals that the tumor has features of a well-differentiated squamous cell carcinoma, such as numerous aggregates of keratin, low mitotic index and minimal pleomorphism. In contrast, low power examination of uPAR-overexpressing tumors reveals an infiltrative lesion with ill-defined borders [2C]. Higher power evaluation shows that the tumor is composed of clusters of hyperchromatic cells with a high nuclear to cytoplasm ratio [2F]. There is cytologic atypia and mitotic figures are easily identified. Unlike uPAR-KD tumors, only focal keratin production is evident. Tumor pathology was evaluated by Dr. Susan Crawford, Northwestern Univ.
