Anaplastic Renal Carcinoma Expressing SV40 T Antigen in a Female TRAMP Mouse

An 8-mo-old female transgenic adenocarcinoma of the mouse prostate (C57BL/6-Tg(TRAMP)8247Ng/J) mouse presented with abdominal distention, lethargy, and serosanguineous vaginal discharge. A large primary renal tumor with metastases to lung and liver was present at necropsy. The tumor was composed of poorly differentiated and crowded epithelial cells forming ducts, acini, and cribriform patterns, with comedonecrosis and frequent bizarre mitoses. Immunohistochemistry revealed that neoplastic cells expressed nuclear SV40 T antigen, confirming aberrant expression of the transgene. In addition, cells were positive for pancytokeratin and negative for synaptophysin and estrogen and progesterone receptors. This report details the first transgene-induced tumor in a female TRAMP mouse.Abbreviations: Tag, large T antigen; TRAMP, transgenic adenocarcinoma mouse prostateThe transgenic adenocarcinoma of the mouse prostate (TRAMP) strain is a genetically engineered mouse strain developed on a C57BL/6 background as a model of human prostate cancer. Human prostatic cancer is characterized by a loss of wildtype tumor protein 53 (TP53) and retinoblastoma (RB1) genes.^9,10,13 The TRAMP model was developed to mimic that mechanism by using the SV40 polyomavirus large T antigen (Tag) to act as an oncogene.¹⁰ Tag protein binds to and inactivates the tumor suppressor proteins TRP53 and RB1. In TRAMP mice, Tag expression is high and limited to the dorsolateral and ventral prostatic lobes, as well as the stromal cells of the seminal vesicles, through the use of the rat probasin promoter (TgrPb-SV40Tag]), and affects the secretory epithelial cells.^6,8,9,20 This gene–promoter combination results in epithelial transformation in vivo under the regulation of androgens and zinc.^9,20 Whereas TRAMP mice on an FVB background readily develop neuroendocrine tumors of the prostate, TRAMP mice with a B6 background are less likely to form neuroendocrine-type prostatic tumors and instead were shown to produce prostatic epithelial origin tumors that can be described as glandular, papillary, or cribriform.²⁰ Seminal vesicle tumors in TRAMP mice do not express Tag within the epithelial component but do express it in the mesenchymal component.²⁰Male TRAMP mice of B6 background begin expressing abnormal differentiation of prostatic epithelial cells at sexual maturity and by 10 to 12 wk of age have mild to severe prostatic hyperplasia with the formation of cribriform structures. By 24 to 30 wk of age, these mice typically develop primary prostatic adenocarcinomas.^9,10 Other abnormalities noted in male TRAMP mice include epithelial–stromal (phyllodes) tumors in the seminal vesicles involving mainly the stroma with low epithelial involvement.^20,22 Female mice are reported as being fertile, with no expression of the transgene or associated neoplasia.¹⁰ This report presents the first documented occurrence of a transgene-expressing neoplasm in a female TRAMP mouse.