LONGITUDINAL COHORT ANALYSIS OF LETHAL PROSTATE-CANCER PROGRESSION INTRANSGENIC MICE

Purpose: Human prostate cancer is variably lethal, shows heterogeneous progression, and exhibits a spectrum of histopathology. Traditional r odent models of prostate cancer lack these characteristics. An alterna tive, autochthonous model of prostate cancer consists of transgenic mi ce which develop prostate cancer due to prostatic expression of SV40 T antigen. Lethal progression of such cancers in individual mice has no t been previously characterized. Studies were undertaken to characteri ze the longitudinal progression of prostate cancers in these transgeni c mice. Methods: A prospective longitudinal cohort study was undertake n to characterize prostate cancer volume, progression, lethality, and histological heterogeneity in a transgenic mouse model of prostatic ad enocarcinoma. Fifty-one transgenic mice were followed prospectively to determine the age at onset of palpable tumor and age at cancer-relate d death. Tumor volume was followed longitudinally by magnetic resonanc e imaging (MRI) in a subset of these mice and lethal cancers were eval uated by histopathology. Results: Primary tumors became palpable at 10 -38 weeks of age. Palpable tumors always preceded lethal progression. Cancer death followed 2-9 weeks later, and age at cancer death varied from 24 to 39 weeks of age. The histopathological changes were heterog eneous. Primary tumors were detectable by MRI before they became detec table by palpation. MRI showed that, analogous to human prostate cance rs, volume of early stage primary tumors did not necessarily predict a ge at cancer death. Conclusion: Prostate cancer in transgenic mice mim ics heterogeneic tumor progression in human prostate cancer, providing a uniquely relevant pre-clinical model. Tumor detection by MRI and pa lpation are valid surrogate measures of tumor progression in this mode l.