Faculty Bibliography

Lymphoid enhancer-binding factor (LEF)1 is a major mediator and a target in canonical Wnt/beta-catenin pathway. Interactions between the androgen receptor (AR) and canonical Wnt pathways have been implicated in the development of the genitourinary organs. Here, we investigated the localization and role of LEF1-positive cells during development of the prostate gland in human and in the murine model. We show that during human prostate development, LEF1 is restricted to the basal epithelial layer of the urogenital sinus. During mouse development, Lef1 is also present in the urogenital mesenchyme in addition to the basal epithelial layer of the urogenital sinus. In the course of elongation and branching of the prostatic ducts, Lef1 is localized to the proliferating epithelium at the distal tips of the buds. Notably, during branching morphogenesis, domains of Lef1 and AR are mutually exclusive. We further employed the TOPGAL reporter strain to examine the dynamics of Wnt signaling in the context of prostate regression upon a 7-d treatment with a competitive AR inhibitor, bicalutamide. We found that Wnt/Lef1-positive basal cells are not dependent upon androgen for survival. Furthermore, upon bicalutamide treatment, Wnt/Lef1-positive basal progenitors repopulated the luminal compartment. We conclude that Wnt/Lef1 activity identifies an androgen-independent population of prostate progenitors, which is important for embryonic development and organ maintenance and regeneration in the adult

PURPOSE: To assess the magnetic resonance imaging (MRI) features of a series of 9 cases of pathologically proven sarcomatoid renal cell carcinoma (SRCC). METHODS: Two radiologists in consensus retrospectively reviewed a spectrum of MRI features of nine cases of SRCC imaged at our institution between 2003 and 2009. RESULTS: SRCC had a mean diameter of 9.9 cm. All cases had an irregular or infiltrative morphology and demonstrated heterogeneous T2 signal intensity and enhancement. Internal necrosis was present in all cases, with four cases demonstrating >50% necrosis. Evidence of aggressive local behavior and/or distant spread was frequently observed. CONCLUSIONS: We have presented the largest case series to our knowledge of the MRI appearance of SRCC, with the lesions tending to appear as large heterogeneous masses with internal necrosis and evidence of aggressive local or distant behavior. However, these imaging features are non-specific, and histology remains necessary to establish the diagnosis

Angiomyolipoma with epithelial cysts (AMLEC) is a rare variant of angiomyolipoma with minimal fat that contains epithelial-lined cysts and may mimic a cystic renal cell carcinoma. While 17 cases have been described in the pathology literature since this entity was first described in 2006, the radiologic appearance was not demonstrated in any of these cases. We report the CT and MRI appearance of AMLEC found incidentally in a patient with lupus nephritis

Merkel cell carcinoma (MCC), a rare aggressive primary cutaneous neuroendocrine carcinoma, occurs on sun-damaged skin, especially in the elderly. Its unique co-expression of cytokeratin 20 (CK20) and neuroendocrine markers, including neuron-specific enolase (NSE), is diagnostic. Most MCCs are located in the dermis, rarely has an intraepidermal component been reported. We report a case of MCC with an intraepidermal component admixed with squamous cell carcinoma in situ (SCCIS). We were able to identify the differences in the immunohistochemical expression pattern between that of the intraepidermal and the dermal components. Most intraepidermal neoplastic cells of MCC in this case showed a less intense immunoreactivity to CK20 and NSE compared to that of dermal neoplastic cells. This case reports an unusual occurrence of combined SCC and MCC that shows both intraepidermal and dermal components

OBJECTIVE: The purpose of this study was to compare a 3D T2-weighted imaging sequence with a conventional multiplanar 2D turbo spin-echo T2-weighted sequence in terms of tumor detection and staging of prostate cancer, as well as image quality. MATERIALS AND METHODS: Before prostatectomy, 38 men (mean age, 60 years) with prostate cancer underwent MRI of the prostate with multiplanar 2D turbo spin-echo T2-weighted sequences (total acquisition time, approximately 11 minutes 4 seconds) and a 3D T2-weighted sampling perfection with application optimized contrasts sequence with different flip angle evolutions (SPACE) (acquisition time, approximately 3 minutes 52 seconds). Two blinded observers in consensus reviewed 2D turbo spin-echo T2-weighted images and SPACE images for detection of peripheral zone cancer, extracapsular extension, and seminal vesicle invasion. The observers also assessed subjective image quality and measured the signal-to-noise ratio (SNR) of normal peripheral zone and tumor-to-peripheral zone contrast. Prostatectomy was used as the reference standard. The diagnostic accuracy of the two sequences was assessed with generalized estimating equations and McNemar tests. The agreement between sequences was assessed with kappa coefficients. A paired Wilcoxon signed rank test was used to compare the subjective image quality, SNR, and tumor-to-peripheral zone contrast of the two sequences. RESULTS: For tumor detection and diagnosis of extracapsular extension, there was substantial agreement between the two sequences (kappa = 0.79, kappa = 0.76) with no difference in sensitivity, specificity, positive predictive value, negative predictive value, accuracy (p = 0.25-1), or image quality (p = 0.937). Images obtained with the 2D turbo spin-echo sequence had a significantly higher SNR ratio for normal peripheral zone (p = 0.0010), but SPACE images had significantly greater tumor-to-peripheral zone contrast (p < 0.0001). CONCLUSION: In comparison with conventional multiplanar 2D turbo spin-echo MRI of the prostate, 3D T2-weighted SPACE MRI was associated with substantial time saving (nearly 8 minutes), had similar image quality and accuracy in the diagnosis of tumor and extracapsular extension, and had better tumor conspicuity

Androgen receptor (AR), a member of the steroid receptor family, is a transcription factor that has an important role in the regulation of both prostate cell proliferation and growth suppression. AR coactivators may influence the transition between cell growth and growth suppression. We have shown previously that the internally spliced ARA70 isoform, ARA70beta, promotes prostate cancer cell growth and invasion. Here we report that the full length ARA70alpha, in contrast, represses prostate cancer cell proliferation and anchorage-independent growth in vitro and inhibits tumor growth in nude mice xenograft experiments in vivo. Further, the growth inhibition by ARA70alpha is AR-dependent and mediated through induction of apoptosis rather than cell cycle arrest. Interestingly, AR with T877A mutation in LNCaP cells decreased its physical and functional interaction with ARA70alpha, facilitating the growth of LNCaP cells. This is consistent with our previous findings that ARA70alpha expression is decreased in prostate cancer cells compared with benign prostate. ARA70alpha also reduced the invasion ability of LNCaP cells. Although growth inhibition by ARA70alpha is AR-dependent, the inhibition of cell invasion is an androgen-independent process. These results strongly suggest that ARA70alpha functions as a tumor suppressor gene