Faculty Bibliography

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

We previously showed that targeted expression of non-receptor tyrosine kinase Etk/BMX in mouse prostate induces prostate intraepithelial neoplasia, implying a possible causal role of Etk in prostate cancer development and progression. Here, we report that Etk is upregulated in both human and mouse prostates in response to androgen ablation. Etk expression seems to be differentially regulated by androgen and interleukin 6 (IL-6), which is possibly mediated by the androgen receptor (AR) in prostate cancer cells. Our immunohistochemical analysis of tissue microarrays containing 112 human prostate tumor samples revealed that Etk expression is elevated in hormone-resistant prostate cancer and positively correlated with tyrosine phosphorylation of AR (Pearson correlation coefficient rho = 0.71, P < 0.0001). AR tyrosine phosphorylation is increased in Etk-overexpressing cells, suggesting that Etk may be another tyrosine kinase, in addition to Src and Ack-1, which can phosphorylate AR. We also showed that Etk can directly interact with AR through its Src homology 2 domain, and such interaction may prevent the association of AR with Mdm2, leading to stabilization of AR under androgen-depleted conditions. Overexpression of Etk in androgen-sensitive LNCaP cells promotes tumor growth while knocking down Etk expression in hormone-insensitive prostate cancer cells by a specific shRNA that inhibits tumor growth under androgen-depleted conditions. Taken together, our data suggest that Etk may be a component of the adaptive compensatory mechanism activated by androgen ablation in prostate and may play a role in hormone resistance, at least in part, through direct modulation of the AR signaling pathway

PURPOSE: To assess the value of quantitative T2 signal intensity (SI) and apparent diffusion coefficient (ADC) to differentiate prostate cancer from post-biopsy hemorrhage, using prostatectomy as the reference. MATERIALS AND METHODS: Forty-five men with prostate cancer underwent prostate magnetic resonance imaging (MRI), including axial T1-weighted imaging (T1WI), T2WI, and single-shot echo-planar image (SS EPI) diffusion-weighted imaging. Two observers measured, in consensus, normalized T2 signal intensity (SI) (nT2, relative to muscle T2 SI), ADC, and normalized ADC (nADC, relative to urine ADC) on peripheral zone (PZ) tumors, benign PZ hemorrhage, and non-hemorrhagic benign PZ. Tumor maps from prostatectomy were used as the reference. Mixed model analysis of variance was performed to compare parameters among the three tissue classes, and Pearson's correlation coefficient was utilized to assess correlation between parameters and tumor size and Gleason score. Receiver-operating characteristic (ROC)-curve analysis was used to determine the performance of nT2, ADC, and nADC for diagnosis of prostate cancer. RESULTS: nT2, ADC, and nADC were significantly lower in tumor compared with hemorrhagic and non-hemorrhagic benign PZ (P < 0.0001). There was a weak but significant correlation between ADC and Gleason score (r = -0.30, P = 0.0119), and between ADC and tumor size (r = -0.40, P = 0.0027), whereas there was no correlation between nT2 and Gleason score and tumor size. The areas under the curve to distinguish tumor from benign hemorrhagic and non-hemorrhagic PZ were 0.97, 0.96, and 0.933 for nT2, ADC, and nADC, respectively. CONCLUSION: Quantitative T2 SI and ADC/nADC values may be used to reliably distinguish prostate cancer from post-biopsy hemorrhage

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

The computed tomographic or magnetic resonance imaging appearance of solitary fibrous tumors of the abdominopelvic cavity has previously only been presented in the English literature as individual case reports. In this article, we present the cross-sectional imaging appearance of 5 such cases, all of which exhibited highly similar imaging features, including well-circumscribed margins, lack of invasion of adjacent structures, and avid enhancement. In view of these shared imaging features, it may be possible to suggest the diagnosis preoperatively. Given their unpredictable biologic behavior with infrequent reports of recurrent or metastatic disease, complete surgical excision and long-term follow-up for these lesions is recommended

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