Faculty Bibliography

BACKGROUND: Interleukin-17 (IL-17) has been demonstrated to promote formation and growth of hormone-naive prostate adenocarcinoma in mice. IL-17's role in development of castration-resistant prostate cancer is unknown. In the present study, we investigated IL-17's role in castration-resistant prostate cancer in a mouse model. METHODS: IL-17 receptor C (IL-17RC) deficient mice were interbred with Pten conditional mutant mice to produce RC(+) mice that maintained IL-17RC expression and RC(-) mice that were IL-17RC deficient. Male RC(+) and RC(-) mice were Pten-null and were castrated at 16 weeks of age when invasive prostate cancer had already formed. At 30 weeks of age, all male mice were analyzed for the prostate phenotypes. RESULTS: RC(-) mice displayed prostates that were smaller than RC(+) mice. Approximately 23% of prostatic glands in RC(-) mice, in contrast to 65% of prostatic glands in RC(+) mice, developed invasive adenocarcinomas. Compared to castrate RC(+) mice, castrate RC(-) mouse prostate had lower rates of cellular proliferation and higher rates of apoptosis as well as lower levels of MMP7, YBX1, MTA1, and UBE2C proteins. In addition, castrate RC(-) mouse prostate had less angiogenesis, which was associated with decreased levels of COX-2 and VEGF. Moreover, castrate RC(-) mouse prostate had fewer inflammatory cells including lymphocytes, myeloid-derived suppressor cells, and macrophages. CONCLUSIONS: Taken together, our findings suggest that IL-17 promotes development of invasive prostate adenocarcinomas under castrate conditions, potentially through creating an immunotolerant and pro-angiogenic tumor microenvironment.

Prostate cancer (PCa) often presents as a multifocal disease with heterogeneity in Gleason score (GS) and genetic alterations. Dominant/index tumor nodule (DN), the largest nodule in a multifocal disease, is presumed to harbor the most aggressive biological behavior and therefore dictate the overall clinical behavior of PCa. In this study, we examined the pathological features of DN and re-evaluated the validity of the "DN" concept in multifocal PCa. A total of 201 consecutive radical prostatectomy specimens were totally submitted and examined. All independent cancer foci were recorded with prognostically important pathological parameters. Unifocal and multifocal disease was present in 25 (12.4 %) and 176 (87.6 %) cases, respectively. In 20 (11.3 %) multifocal cases, the highest GS, the largest tumor volume (TV), and extraprostatic extension (EPE) did not concur in the same tumor nodules. Non-DNs had a higher GS and EPE in 13 cases each and had both the highest GS and EPE in 5 cases. In the majority of multifocal prostate cancer (88.7 %), DNs have the highest GS and EPE. In these cases, DN is still a valid concept and can be used for assigning overall GS and procuring tissue for research. However, in a significant number of cases (11.3 %), the largest TV, the highest GS, and EPE did not concur in the same tumor nodules. In these cases, pathologists should de-emphasize the concept of DN. Instead, they should place the emphasis on the multifocal nature of the disease and document the pathological features of all independent tumor foci that have the largest TV, the highest GS, and EPE.

The microbiome is a new center of attention for studies on the pathogenesis of human disease by focusing on the alterations of all microorganisms living in a particular site or system of human body, referred as microbiota. Evidence suggests that microbiota could contribute to the pathogenesis of a number of chronic diseases, including cancers, both locally and remotely. Multiple mechanisms have been proposed and/or proven for the microbiota's role in tumorigenesis, such as via induction of chronic inflammation, genotoxicity, bacterium-mediated cell proliferation, and activation of procarcinogens. Emerging data suggest that indigenous microbiota in the urinary tract may play an important role in the tumorigenesis of urothelial carcinoma, similar to other tumors. Future studies are needed to adequately define the microbiota composition and correlate its change with urothelial carcinoma.

INTRODUCTION: To assess impact of size of regions-of-interest (ROI) on differentiation of RCC and renal cysts using multi-phase CT, with focus on differentiating papillary RCC (pRCC) and cysts given known hypovascularity of pRCC. METHODS: 99 renal lesions (23 pRCC, 47 clear-cell RCC, 7 chromophobe RCC, 22 cysts) underwent multi-phase CT. Subjective presence of visual enhancement was recorded for each lesion. Whole-lesion (WL) ROIs, and small (