UAP1 is overexpressed in prostate cancer and is protective against inhibitors of N-linked glycosylation.

Prostate cancer is the second most common cause of cancer-associated deaths in men, and signaling via a transcription factor called androgen receptor (AR) is an important driver of the disease. Consequently, AR target genes are prominent candidates to be specific for prostate cancer and also important for the survival of the cancer cells. Here we assess the levels of all hexosamine biosynthetic pathway (HBP) enzymes in 15 separate clinical gene expression data sets and identify the last enzyme in the pathway, UDP-N-acetylglucosamine pyrophosphorylase 1 (UAP1), to be highly overexpressed in prostate cancer. We analyzed 3261 prostate cancers on a tissue microarray and found that UAP1 staining correlates negatively with Gleason score (P=0.0039) and positively with high AR expression (P<0.0001). Cells with high UAP1 expression have 10-fold increased levels of the HBP end-product, UDP-N-acetylglucosamine (UDP-GlcNAc). UDP-GlcNAc is essential for N-linked glycosylation occurring in the endoplasmic reticulum (ER) and high UAP1 expression associates with resistance against inhibitors of N-linked glycosylation (tunicamycin and 2-deoxyglucose) but not with a general ER stress-inducing agent, the calcium ionophore A23187. Knockdown of UAP1 expression re-sensitized cells towards inhibitors of N-linked glycosylation, as measured by proliferation and activation of ER stress markers. Taken together, we have identified an enzyme, UAP1, which is highly overexpressed in prostate cancer and protects cancer cells from ER stress conferring a growth advantage.

High Nr-CAM expression is associated with favorable phenotype and late PSA recurrence in prostate cancer treated by prostatectomy.

BACKGROUND: Neuron-glia-related cell-adhesion molecule (Nr-CAM) is another potential membrane-bound target molecule for specific prostate cancer therapy. The role of Nr-CAM in normal and neoplastic prostate tissue has not been extensively studied. The aim of our study is to evaluate the prevalence of Nr-CAM expression in prostate cancer and to explore its association with phenotype and clinical disease course. METHODS: A preexisting tissue microarray including more than 3000 prostate cancers that underwent prostatectomy at our center with clinical follow-up data was used. The tissue microarray (TMA) was immunhistochemically stained for Nr-CAM. RESULTS: A total of 2883 (88.4%) of tumor samples were interpretable in our TMA analysis. Membranous Nr-CAM staining was seen in 1418 (49.2%) of 2883 analyzable cases. According to predefined criteria, staining was considered weak in 778 (27.0%), moderate in 412 (14.3%) and strong in 228 (7.9%) cancers. Significant associations were found with pathological tumor stage (P=0.0015), Gleason grade (P=0.0003), nodal stage (P=0.0061), preoperative PSA (P=0.0138) and prolonged PSA recurrence-free survival (P<0.0001). CONCLUSIONS: Nr-CAM expression is frequent in prostate cancer. High level of Nr-CAM expression is associated with favorable tumor phenotype and reduced risk of PSA recurrence. The abundant presence of Nr-CAM in prostate cancer epithelium makes Nr-CAM a potential target of therapy.

[Primary diffuse neurofibroma of the urinary bladder: a rare case report and review of the literature]. / Primäres diffuses Neurofibrom der Harnblase : Ein seltener Fallbericht und Literaturübersicht.

Diffuse neurofibromas are benign mesenchymal tumours with nerve sheath differentiation. Only a few cases have been reported in the urinary bladder. We present a well-documented case report of a 62-year-old man presenting with gross haematuria and histopathological confirmation of a diffuse neurofibroma. We further reviewed the current literature with regard to clinical features and treatment options.

HER-2/neu analysis in breast cancer bone metastases.

BACKGROUND: HER-2 is the target for antibody-based treatment of breast cancer (trastuzumab), which is highly successful in both advanced disease and the adjuvant setting. HER-2 can be analysed by fluorescence in situ hybridisation (FISH) for gene amplification or immunohistochemistry (IHC) for protein overexpression. AIM: As both methods are known to be influenced by previous tissue processing, to analyse the applicability of both FISH and IHC to decalcified bone metastases of breast cancer. METHODS: A tissue microarray (TMA) was constructed from 149 breast cancer bone metastases. Consecutive TMA sections were analysed by FISH (PathVysion) and IHC (HercepTest). RESULTS: FISH analysis was interpretable in 113 (85.0%) cases. Amplification was seen in 14 (12.4%) interpretable metastases. HER-2 positivity on IHC analysis was 3+ in 9.8% of cases and 2+ in 11.3%. A comparison of the two techniques revealed high concordance. Of the 14 cases of amplification, 10 (71%) showed 3+ IHC staining, two (14%) showed 2+, one (7%) showed 1+, and one (7%) showed 0+. Three of the four amplified cases that did not show 3+ IHC staining had an equivocal FISH result, with a HER-2/centromere 17 ratio of 1.8-2.2. Of the 13 cases that showed IHC 3+ staining, amplification was present in 10 (77%). CONCLUSIONS: HER-2 FISH analysis has an excellent success rate in highly standardised EDTA-decalcified bone metastases, suggesting that this method is easily applicable to decalcified tissues. The high concordance between IHC and FISH suggests that HER-2 IHC may be equally applicable to EDTA-treated tissues as to the usual formalin-fixed tissues.