Morphological Characterization of Spindle Cell Tumors Induced in Transgenic Tg.AC Mouse Skin

Abstract

ABSTRAC~Transgenic Tg.AC mice carry a v-Ha-rus coding region flanked by a <-globin promoter and an SV40 polyadenylation signal sequence. These mice respond to carcinogens by developing epidermal papillomas. In some cascs, malignancies develop at the sites of these papillomas. Various patterns of squamous cell differentiation were observed in these malignancies. One malignancy that developed at the site of the papillomas was composed of bundles of spindle cells. This lesion is difficult to distinguish from fibrosarcomas by light microscopy. We characterized 16 of these malignancies (tentatively classified as spindle cell tumors) to determine if they were of epithelial or mesenchymal origin. Papillomas were induced in Tg.AC mice by full thickness wounding, 12-0-tetradecanoyl-13-phorbol acetate treatment. or ultraviolet radiation. With time, some papillomas became broad-based, downwardly invading lesions. These lesions were examined by light microscopy with.immunohistochemica1 analysis for cytokeratins and by electron microscopy. Immunohistochemical examination with a polyclonal anti-cytokeratin antibody demonstrated various degrees of keratin staining in all tumors examined. Attenuated desmosomes were also observed in these lesions by electron microscopy. These results indicate an epithelial origin for these malignancies; therefore, they should be classified as spindle cell carcinomas.

Proliferative and Non-Proliferative Lesions of the Rat and Mouse Integument

“…without penetration of the basal membrane) have not been reported in rodents. ( 7 Bader et al, 1993; 14 Bogovski, 1994; 28 Deerberg et al, 1986; 32 Elwell et al, 1990; 33 Evans et al, 1997; 34 Faccini et al, 1990; 38 Frith and Ward, 1988; 47 Greaves and Faccini, 1984; 53 Hasegawa et al, 1989; 57 Hirose, 1989; 75 Maita et al, 1988; 97 Okum et al, 1988; 99 Peckham and Heider, 1999; 105 Rehm et al, 1989; 116 Squire et al, 1978; 132 Weiss and Frese, 1974; 141 Zackheim et al, 1990; 144 Zwicker et al, 1992 ; 17 Bruner et al, 2001; 4 Asano et al, 1998)…”

Biological, cellular, and molecular characteristics of an inducible transgenic skin tumor model: a review

“…Tg.AC mice can develop cutaneous malignancies, the sites of which have always been associated with spontaneous or induced papillomas (Hansen et al, 1996;Asano et al, 1998). Malignancies are primarily either squamous cell carcinomas or spindle cell carcinomas (Hansen et al, 1996), although malignant fibrous histiocytoma-like (MFH-like) spindle cell tumors have been reported (Cardiff et al, 1993;Asano et al, 1998).…”

“…Malignancies are primarily either squamous cell carcinomas or spindle cell carcinomas (Hansen et al, 1996), although malignant fibrous histiocytoma-like (MFH-like) spindle cell tumors have been reported (Cardiff et al, 1993;Asano et al, 1998). Based on subsequent immunohistochemical staining for keratins, as well as the presence of desmosomes, the spindle cell carcinomas have been shown to be of epithelial origin (Asano et al, 1998). Transgene expression, while usually found at the basal region of papillomas, may be found throughout spindle or squamous cell carcinomas (Hansen et al, 1996).…”

Delayed foreign body granuloma secondary to an abandoned cardiac pacemaker wire

“…Indeed, in animal models SV40-infected cells might trigger the development of MFH. 9 A role for a virus has never been demonstrated in human MFH but remains possible according to this experimental report, considering the immunodeficiency associated with HIV infection. Conversely, the metastatic evolution observed in our patient seems to be related more to the large size of the primary tumour than to the immune failure itself, as the delay of metastasis appearance and metastasis to the lung are usual for this subset of tumour…”