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BACKGROUND Serum/glucocorticoid-regulated kinase 1 (SGK1), a known target of the androgen receptor (AR) and glucocorticoid receptor (GR), is reported to enhance cell survival. This study sought to better define the role of SGK1 and GR in prostate cancer. METHODS Immunohistochemistry was performed for AR, GR, and SGK1 on primary prostate cancers (n = 138) and 18 prostate cancers from patients treated with androgen deprivation therapy. Relative staining intensity was compared utilizing a Fisher's exact test. Univariate analyses were performed using log-rank and chi-squared tests to evaluate prostate cancer recurrence with respect to SGK1 expression. RESULTS SGK1 expression was strong (3+) in 79% of untreated cancers versus 44% in androgen-deprived cancers (P = 0.003). Conversely, GR expression was present in a higher proportion of androgen-deprived versus untreated cancers (78% vs. 38%, P = 0.002). High-grade cancers were nearly twice as likely to have relatively low (0 to 2+) SGK1 staining compared to low-grade cancers (13.8% vs. 26.5%, P = 0.08). Low SGK1 expression in untreated tumors was associated with increased risk of cancer recurrence (adjusted log-rank test P = 0.077), 5-year progression-free survival 47.8% versus 72.6% (P = 0.034). CONCLUSIONS SGK1 expression is high in most untreated prostate cancers and declines with androgen deprivation. However, these data suggest that relatively low expression of SGK1 is associated with higher tumor grade and increased cancer recurrence, and is a potential indicator of aberrant AR signaling in these tumors. GR expression increased with androgen deprivation, potentially providing a mechanism for the maintenance of androgen pathway signaling in these tumors. Further study of the AR/GR/SGK1 network in castration resistance. Prostate 72:157–164, 2012. © 2011 Wiley Periodicals, Inc.

Primary extra-nodal marginal zone B cell lymphoma (Ex-MZBCL) or mucosa-associated lymphoid tissue (MALT) lymphoma of the cranial dura is a rare but well-known entity. We describe a 58-year-old woman with primary MALT lymphoma of the spinal dura causing extreme thickening of the dura and spinal cord compression who initially presented with acute spinal cord compression from a chronic epidural lesion. She was treated with surgery and radiotherapy and diagnosed with a mature B-cell lymphoma based on gene rearrangement studies. Two years following the completion of radiotherapy, she presented with an increase in the size of the residual mass that was suggestive of an epidural lesion. On re-exploration, no epidural lesion was found; however, the dura was extremely thickened causing spinal cord compression. Clinical course, histological evaluation, immunostaining and gene rearrangement studies resulted in a final diagnosis of primary Ex-MZBCL of the spinal dura. To our knowledge, this is the first report of Ex-MZBCL in the spinal dura. This diagnosis should be considered when evaluating spinal cord lesions in patients with primary central nervous system (CNS) lymphoma, especially recurrent lesions, since this group of tumors carries a favorable outcome compared to other primary CNS lymphomas.

Background Antibody-mediated rejection (AMR) is associated with poorer outcomes in cardiac transplantation. The clinical diagnosis of AMR has been confirmed by immunofluorescence for C4d on fresh-frozen cardiac tissue. Immunohistochemistry (IHC) has been suggested as a more practical diagnostic tool because it can be performed on routine paraffin-embedded tissue. There are few published data about hemodynamics and C4d staining. We prospectively performed C4d staining on endomyocardial biopsies (EMBs) and present the pattern of tissue staining and its correlation with intracardiac hemodynamics. Methods EMBs were evaluated by IHC for C4d staining and graded for cellular rejection using ISHLT criteria on hematoxylin-and-eosin–stained sections. Hemodynamic measurements were taken concurrently. Staining for C4d was described as absent, present with serum staining, or present with only tissue staining. The pattern of tissue staining was categorized by location of staining and correlated with intracardiac hemodynamics. Patient demographics, cytomegalovirus status, panel-reactive antibody levels and hemodynamics were analyzed by analysis of variance and chi-square statistics. Results Of the 400 EMBs, 50 had no C4d staining, 330 had tissue and serum staining, whereas 20 had only tissue staining. Forty EMBs had endothelial staining, including 35 with serum and 5 with isolated tissue staining. Endothelial staining correlated with higher intracardiac pressures. Conclusions IHC staining for C4d has been suggested for the diagnosis of AMR. Our data suggest there is a high rate of background C4d staining, but endothelial staining correlates with poorer hemodynamics. Methods for IHC staining and interpretation need to be standardized for widespread use and clinical studies.

vascular macrophages were detected despite 35 grade 1R biopsies (in 10 patients; untreated) and 3 episodes of Grade 2R rejection (in three patients; treated). Conclusions: Capillary deposition of C4d occurs ‘normally’ in EMBs after cardiac Tx. C3d staining was more frequent and persistent. Intracapillary macrophages were not seen even in the presence of ACR and therefore could be a more specific marker of humoral rejection. The ‘normal’ pattern of complement deposition must be considered when assessing biopsies for AMR.