Faculty Bibliography

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: Tumors of the kidney are uncommon in children and young adults. Accurate classification is crucial for both prognostication and therapeutic intervention. However, majority of the tumors in this age group have unusual morphology that renders classification challenging. Tubulopapillary architecture is one of the most common morphological patterns observed in renal tumors of children and young adults. METHODS: A patient with epithelial predominant Wilms tumor was reported. Differential diagnosis of renal tumors with tubulopapillary morphology was discussed with an emphasis on the histological and immunohistochemical features, and the literature was reviewed. RESULTS: A 25 year-old female patient presented with bilateral multilocular cystic masses. She underwent right radical nephrectomy and left partial nephrectomy. The pathological examination revealed a tumor with tubulopapillary architecture which was lined with low columnar epithelial cells. During the work-up of this case, several entities were considered and ruled out by careful gross, microscopic examination and prudent use of immunohistochemistry. The tumor cells were positive for WT-1, and variably positive for cytokeratin AE1/3, CD56, CD57, and negative for cytokeratin 7 and EMA. Fluorescent in-situ hybridization revealed no gain of chromosome 7 and 17. A diagnosis of epithelial predominant adult Wilms tumors was rendered for both kidneys. The patient received systemic chemotherapy and radiation to the remnant left kidney and was free of disease three years after the initial surgery. CONCLUSION: The differential diagnosis of renal tumors with tubulopapillary features in children and young adults include papillary renal cell carcinoma, metanephric adenoma, epithelial predominant Wilms tumor, translocation renal cell carcinoma and metastatic adenocarcinoma to the kidney. An accurate classification relies on careful examination of clinical and pathological features and immunohistochemical characteristics.

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 ERalpha and ERbeta in prostate cancer (PCa). This study characterizes the expression patterns of ERalpha and ERbeta in tumor-associated stroma in association with various clinicopathological factors of importance in PCa prognosis and treatment. DESIGN: Immunohistochemistry was performed using antibodies against ERalpha and ERbeta to characterize their expression patterns in PCa tissue. Stromal ER levels (ERalpha and ERbeta) 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 ERalpha and ERbeta were significantly lower in tumor-associated stroma than stroma surrounding benign prostatic glands on the same tissue section (ERalpha: p<0.01; ERbeta: p=0.01). When correlated with clinicopathological factors, the level of ERalpha expression in tumor-associated stroma showed a positive correlation with Gleason score (R(2)=0.8638). The expression of ERalpha was higher in PCa with advanced tumor stage (p=0.05) and not significantly different in extraprostatic extension (p>0.05). The level of ERbeta 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 ERalpha and ERbeta expression in the tumor-associated stroma of PCa. However, the level of ERalpha expression in tumor-associated stroma shows a positive correlation with cancer differentiation and tumor stage.

Large cell neuroendocrine carcinoma of the prostate (LCNEC), de novo in particular, is an extremely rare entity that has only been described in the literature in case reports. Historically, the majority of the cases of LCNEC reported in the literature represent typical prostatic adenocarcinomas that transformed after long standing androgen deprivation therapy (ADT). These cases were admixed with histological areas of usual adenocarcinoma and showed hybrid features of both neuroendocrine and usual adenocarcinoma. Here we present a case of an LCNEC without admixed areas of usual prostatic adenocarcinoma arising de novo in a patient without prior history of hormonal therapy. The tumor also shows morphologic evidence of neuroendocrine differentiation; composed of large sheets and nests of cells with moderate amphophilic cytoplasm with peripheral palisading, and vesicular clumpy chromatin with prominent nucleoli. The carcinoma's prostatic origin is indicated by positive immunohistochemical staining for PSA, PAP, PSMA, racemase, and Nkx3.1. Diffusely positive staining for chromogranin and synaptophysin, as well as the presence of secretory granules in the cytoplasm of the tumor cells demonstrated by electron microscopy supports the NE differentiation. NE prostate cancer usually does not express AR and is refractory to ADT therapy while AR and ERG are positive in this case. In summary, we report a de novo LCNEC of the prostate with review of literature, in particular, clinical implications.

OBJECTIVE. The purpose of this article is to evaluate the utility of various morphologic and quantitative MRI features in differentiating central renal cell carcinoma (RCC) from renal pelvic urothelial carcinoma. MATERIALS AND METHODS. Sixty patients (39 men and 21 women; mean [+/- SD] age, 65 +/- 14 years; 48 with central RCC and 12 with renal pelvic urothelial carcinoma) who underwent MRI, including diffusion-weighted imaging (b values, 0, 400, and 800 s/mm(2)) and dynamic contrast-enhanced imaging, before histopathologic confirmation were included. Tumor T2 signal intensity and apparent diffusion coefficients (ADCs) were measured and normalized to muscle and CSF (hereafter referred to as normalized T2 signal and normalized ADC, respectively) and then were compared using receiver operating characteristic analysis. Also, two blinded radiologists independently assessed all tumors for various qualitative features, which were compared with the Fisher exact test and unpaired Student t test. RESULTS. Urothelial carcinoma exhibited significantly lower normalized ADC than did RCC (p = 0.008), but no significant difference was seen in ADC or normalized T2 signal intensity (p = 0.247-0.773). Normalized ADC had the highest area under the curve (0.757); normalized ADC below an optimal threshold of 0.451 was associated with sensitivity of 83% and specificity of 71% for diagnosing urothelial carcinoma. Features that were significantly more prevalent in urothelial carcinoma included global impression of urothelial carcinoma, location centered within the collecting system, collecting system defect, extension to the ureteropelvic junction, preserved renal shape, absence of cystic or necrotic areas, absence of hemorrhage, homogeneous enhancement, and hypovascularity (all p < 0.033). Increased T1 signal intensity suggestive of hemorrhage was significantly more prevalent in RCC (p = 0.02). Interreader agreement for the subjective features ranged from 61.7% to 98.3%. CONCLUSION. In addition to various qualitative MRI parameters, normalized ADC has utility in differentiating central RCC from renal pelvic urothelial carcinoma. Such differentiation may assist decisions regarding possible biopsy and treatment planning.

OBJECTIVE. The purpose of this study was to assess associations between quantitative MRI metrics and pathologic indicators of aggressiveness of urothelial carcinoma of the bladder. MATERIALS AND METHODS. In this retrospective biinstitutional study, 37 patients (28 men and nine women; mean age, 73 +/- 12 years) who underwent pelvic MRI including diffusion-weighted imaging (b values 0, 400, and 800 s/mm(2)) and T2-weighted imaging before transurethral resection or cystectomy for urothelial carcinoma of the bladder were identified. Tumor diameter (measured on T2-weighted imaging), normalized T2 signal intensity (to muscle; hereafter labeled normalized T2) and apparent diffusion coefficient (ADC) were measured for all tumors. Mann-Whitney test and receiver operating characteristic analyses were used to identify associations between these metrics and histopathologic tumor stage and grade. RESULTS. Thirty-seven tumors were assessed (mean size, 35 +/- 23 mm; range 8-88 mm). At histopathologic analysis, 16 of 37 (43%) tumors were stage T2 or greater and 21 of 37 (57%) were stage T1 or lower, whereas 34 of 37 (92%) were high grade and three of 37 (8%) were low grade. High-stage (>/= T2) tumors showed greater tumor diameter, lower normalized T2, and lower ADC (p = 0.005-0.032) than low-stage (