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Context.--While biopsies are now increasingly being performed for the diagnosis of renal cortical neoplasms, the influence of the rendered pathological diagnoses on the clinical management is only rarely documented. Objectives.--To report our experience with consecutively performed renal biopsies and the potential impact of the diagnosis on subsequent clinical management. Design.--Material from needle biopsies performed consecutively at our institution between 2006 and 2011 was reviewed. The influence of the reported pathology results on the clinical management was determined from patient follow-up medical record review. Results.--In total, 218 percutaneous biopsies for renal masses were performed during this period. Among them, 181 (83%) yielded neoplastic tissue, including 81 clear cell renal cell carcinomas, 29 low-grade oncocytic neoplasms, 7 papillary renal cell carcinomas, 5 clear cell papillary renal cell carcinomas, 5 angiomyolipomas, and 14 urothelial carcinomas. Fourteen additional cases (6%) contained lesional material from clinically known nonneoplastic processes, for a total diagnostic yield of 89%. Twenty-three (11%) were nonrepresentative of lesional tissue. In 10 of these, repeat biopsies or resections established the diagnosis of renal tumors. Biopsy diagnosis was confirmed in 29 of 30 cases (97%) on subsequent nephrectomy. Following the biopsy diagnosis, there were significant differences in the clinical management; overall, 79% of clear cell renal cell carcinomas received therapeutic interventions, and 17% were put on active surveillance. In contrast, 77% of the benign or low-grade lesions were put on active surveillance. Conclusions.--Accurate and specific diagnosis can be rendered on renal core biopsy in most renal tumors, and the biopsy diagnosis can have a definitive role in their clinical management. (Arch Pathol Lab Med. 2014;138:1673-1679; doi: 10.5858/arpa.2013-0574-0A), With increased popularity and the improvements in imaging modalities, up to 70% of renal cortical tumors are now discovered incidentally, most with a median tumor size of less than 4 [...]

Androgen receptor (AR), a steroid hormone receptor, is critical for prostate cancer growth. However, activation of AR by androgens can also lead to growth suppression and differentiation. Transcriptional cofactors play an important role in this switch between proliferative and anti-proliferative AR target gene programs. Transducin b-like-related protein 1 (TBLR1), a core component of the nuclear receptor corepressor complex, shows both corepressor and coactivator activities on nuclear receptors, but little is known about its effects on AR and prostate cancer. We characterized TBLR1 as a coactivator of AR in prostate cancer cells and determined that the activation is dependent on both phosphorylation and 19S proteosome. We showed that TBLR1 physically interacts with AR and directly occupies the androgen-response elements of the affected AR target genes in an androgen-dependent manner. TBLR1 is primarily localized in the nucleus in benign prostate cells and nuclear expression is significantly reduced in prostate cancer cells in culture. Similarly, in human tumor samples, the expression of TBLR1 in the nucleus is significantly reduced in the malignant glands compared with the surrounding benign prostatic glands (P<0.005). Stable ectopic expression of nuclear TBLR1 leads to androgen-dependent growth suppression of prostate cancer cells in vitro and in vivo by selective activation of androgenregulated genes associated with differentiation (e.g. KRT18) and growth suppression (e.g. NKX3-1), but not cell proliferation of the prostate cancer. Understanding the molecular switches involved in the transition from AR-dependent growth promotion to AR-dependent growth suppression will lead to more successful treatments for prostate cancer. [ABSTRACT FROM AUTHOR]

Global microRNA (miRNA) profile may predict prostate cancer (PCa) behaviors. In this study, we examined global miRNA expression by miRNA profiling as well as specific miRNA expression levels in PCa epithelium and stroma by in situ hybridization (ISH) and correlated with various clinicopathological features. We first performed comprehensive miRNA profiling on 27 macrodissected cases of PCa by miRNA microarray. A total of 299 miRNAs were significantly dysregulated in high grade and advanced stage PCa. We demonstrated that PCa can be readily classified into high grade/stage and low-grade/stage groups by its global miRNA expression profile. Next, we examined the expression of several selected dysregulated miRNAs, including let-7c, miR-21, miR-27a, miR-30c, and miR-219, in PCa by ISH. The levels of miRNA expression in epithelial and stromal cells were scored semiquantitatively and compared with clinicopathological features, including age, race, Gleason score, stage, PSA recurrence, metastasis, hormone resistance and survival. We found that the expression of miR-30c and miR-219 were significantly down-regulated in PCa. miR-21 and miR-30c were significantly down-regulated in PCa in African Americans compared to Caucasian Americans. In addition, down-regulation of let-7c, miR-21, miR-30c, and miR-219 are associated with metastatic disease. Furthermore, down-regulation of miR-30c and let-7c are significantly associated with androgen-dependent PCa. In PCa stromal cells, let-7c downregulation is significantly associated with extraprostatic extension. Our data suggest that selected miRNAs may serve as potential biomarkers to predict cancer progression.

Background: Recently there has been an increased interest in the role of tumor-associated stroma in prostate tumorigenesis, but little is known about the respective roles of stomal ERα and ERβ in prostate cancer (PCa). This study characterizes the expression patterns of ERα and ERβ in tumor-associated stroma in association with various clinicopathological factors of importance in PCa prognosis and treatment., Design: Immunohistochemistry was performed using antibodies against ERα and ERβ to characterize their expression patterns in PCa tissue. Stromal ER levels (ERα and ERβ) on tissue sections (n=47), were compared between tumor associated stroma and adjacent benign associated stroma. Immunohistochemistry was also performed on a PCa tissue microarray (TMA) (n=177) to correlate stromal expression with various clinicopathological parameters. The levels of ER nuclear expression were scored semi-quantitatively., Results: The expression levels of both ERα and ERβ were significantly lower in tumor-associated stroma than stroma surrounding benign prostatic glands on the same tissue section (ERα: p<0.01; ERβ: p=0.01). When correlated with clinicopathological factors, the level of ERα expression in tumor-associated stroma showed a positive correlation with Gleason score (R(2)=0.8638). The expression of ERα was higher in PCa with advanced tumor stage (p=0.05) and not significantly different in extraprostatic extension (p>0.05). The level of ERβ expression in tumor-associated stroma was decreased in patients older than 60 years compared to younger patients (p=0.01)., Conclusion: This study demonstrates significant down-regulation of ERα and ERβ expression in the tumor-associated stroma of PCa. However, the level of ERα expression in tumor-associated stroma shows a positive correlation with cancer differentiation and tumor stage.

Kaposi sarcoma-associated herpes virus (KSHV) infects B-cells and is found in non-Hodgkin lymphoma (NHL) B-cell tumors and could therefore contribute to the occurrence of NHL. We performed a nested case-control study including 155 incident NHL cases and matched noncancer controls. Pre-NHL serum was tested for KSHV DNA and antibodies. Serum KSHV DNA was more common in cases than controls (14% versus 6%, P = 0.03), but after adjustment, the difference was not significant. Epstein-Barr virus serum DNA was similarly unassociated with NHL as were KSHV antibodies. KSHV is not a primary cause of NHL in HIV-infected men who have sex with men.