Clinical relevance of gene expression in localized and metastatic prostate cancer exemplified by FABP5.

PURPOSE: Fatty acid-binding protein 5 (FABP5), a transport protein for lipophilic molecules, has been proposed as protein marker in prostate cancer (PCa). The role of FABP5 gene expression is merely unknown. METHODS: In two cohorts of PCa patients who underwent radical prostatectomy (n = 40 and n = 57) and one cohort of patients treated with palliative transurethral resection of the prostate (pTUR-P; n = 50) FABP5 mRNA expression was analyzed with qRT-PCR. Expression was correlated with clinical parameters. BPH tissue samples served as control. To independently validate findings on FABP5 expression, three microarray and sequencing datasets were reanalyzed (MSKCC 2010 n = 216; TCGA 2015 n = 333; mCRPC, Nature Medicine 2016 n = 114). FABP5 expression was correlated with ERG-fusion status, TCGA subtypes, cancer driver mutations and the expression of druggable downstream pathway components. RESULTS: FABP5 was overexpressed in PCa compared to BPH in the cohorts analyzed by qRT-PCR (radical prostatectomy p = 0.003, p = 0.010; pTUR-P p = 0.002). FABP5 expression was independent of T stage, Gleason Score, nodal status and PSA level. FABP5 overexpression was associated with the absence of TMPRSS2:ERG fusion (p < 0.001 in TCGA and MSKCC). Correlation with TCGA subtypes revealed FABP5 overexpression to be associated with SPOP and FOXA1 mutations. FABP5 was positively correlated with potential drug targets located downstream of FABP5 in the PPAR-signaling pathway. CONCLUSION: FABP5 overexpression is frequent in PCa, but seems to be restricted to TMPRESS2:ERG fusion-negative tumors and is associated with SPOP and FOXA1 mutations. FABP5 overexpression appears to be indicative for increased activity in PPAR signaling, which is potentially druggable.

[Ectopic thymic tissue and ectopic thymic tumors]. / Ektopien des Thymus und ektope Thymustumoren.

Ectopic thymic tissue outside its core position in the antero-superior mediastinum is quite common owing to the complexity of embryonal thymus development, whereby reported prevalence values (1 to 90%) are heavily dependent on the method of investigation and the intensity of the workup. The debated prevalence and relevance of ectopic thymic tissue and its accessibility underlie the ongoing discussion whether modern, minimally invasive thymectomy strategies can match the proven benefit of the radical transsternal thymectomy procedure for the treatment of Myasthenia gravis. In this context, the following article covers the etiology, prevalence, and location of normal-looking, reactive, and neoplastic ectopic thymic tissue. Furthermore, ectopic tissues and tumors inside or adjacent to the thymus are mentioned.

Prognostic Value of Molecular Breast Cancer Subtypes based on Her2, ESR1, PGR and Ki67 mRNA-Expression in Muscle Invasive Bladder Cancer.

INTRODUCTION: Gene expression analyses have identified similarities between bladder and breast cancer, where clinical risk stratification is based on Her2, ESR1, PGR and Ki67 expression. The aim of the study was to assess the respective marker gene expression in patients treated with radical cystectomy for muscle-invasive bladder cancer (MIBC) and to evaluate the applicability of breast cancer subtypes for MIBC risk stratification. MATERIALS & METHODS: 102 patients treated with radical cystectomy for MIBC were assessed. Using routine FFPE tissue and an IVD validated kit, mRNA expression was measured by single step RT-qPCR. Partition test were employed to define cut-off values for high or low marker gene expression. Association of expression with outcome was assessed using Kaplan-Meier analysis and multivariate cox regression analysis. Finally, we performed validation of our results in the MD-Anderson cohort (n=57). RESULTS: Cancer specific survival (CSS) was impaired in patients with high gene expression of Her2 (P=0.0009) and ESR1 (P=0.04). In the multivariate regression model Her2 expression remained significant for the prediction of CSS (HR=2.11, CI 1.11-4.21, P=0.024). Furthermore, molecular stratification by breast cancer subgroups was significant (P=0.023) for CSS prediction. Especially the differentiation between Her2-positive and Luminal A (HR=4.41, CI 1.53-18.71, P=0.004) and Luminal B (HR=1.96, CI 0.99-4.08, P=0.053) respectively was an independent prognostic parameter for CSS. External validation resulted in comparable risk stratification with differences in fractional subgroups distribution. CONCLUSION: Gene expression of Her2, ESR1, PGR, Ki67 and corresponding breast cancer subtypes allow a risk-stratification in MIBC, whereby Her2 overexpressing tumors reveal a particularly poor prognosis.

Diagnostic Performance of Contrast Enhanced Pulmonary Computed Tomography Angiography for the Detection of Angioinvasive Pulmonary Aspergillosis in Immunocompromised Patients.

Invasive pulmonary aspergillosis (IPA) is one of the major complications in immunocompromised patients. The mainstay of diagnostic imaging is non-enhanced chest-computed-tomography (CT), for which various non-specific signs for IPA have been described. However, contrast-enhanced CT pulmonary angiography (CTPA) has shown promising results, as the vessel occlusion sign (VOS) seems to be more sensitive and specific for IPA in hematologic patients. The aim of this study was to evaluate the diagnostic accuracy of CTPA in a larger cohort including non-hematologic immunocompromised patients. CTPA studies of 78 consecutive immunocompromised patients with proven/probable IPA were analyzed. 45 immunocompromised patients without IPA served as a control group. Diagnostic performance of CTPA-detected VOS and of radiological signs that do not require contrast-media were analyzed. Of 12 evaluable radiological signs, five were found to be significantly associated with IPA. The VOS showed the highest diagnostic performance with a sensitivity of 0.94, specificity of 0.71 and a diagnostic odds-ratio of 36.8. Regression analysis revealed the two strongest independent radiological predictors for IPA to be the VOS and the halo sign. The VOS is highly suggestive for IPA in immunocompromised patients in general. Thus, contrast-enhanced CTPA superior over non-contrast_enhanced chest-CT in patients with suspected IPA.

Novel insights into a reputably irreversible process: combined mRNA and miRNA profiling of tissue from vesicourethral anastomotic stenosis after radical prostatectomy.

PURPOSE: Until recently, tissue fibrosis-ultimately leading to permanent scaring-has been considered an irreversible process. However, recent findings indicate that it may be reversible after all. Vesicourethral anastomotic stenosis (VUAS) as fibrous narrowing is a frequent complication after radical prostatectomy with high recurrence rates and requires invasive treatment. The pathophysiology is poorly understood. Therefore, a combined mRNA and miRNA transcription profiling in tissue from VUAS was performed using nCounter technology. METHODS: To assess tissue morphology and fiber composition, histochemical staining was performed. RNA expression of healthy and fibrotic tissue of twelve patients was analyzed using the human miRNA panel v3 and mRNA PanCancer pathway panel on the nCounter gene1 system and qRT-PCR. Differential expression data analysis was performed using the nSolver software implementing the R-based advanced pathway analysis tool. miRWalk2.0 was used for miRNA target prediction. RESULTS: More linearized tissue architecture, increased collagens, and decreased elastic fibers were observed in VUAS samples. 23 miRNAs and 118 protein coding genes were differentially expressed (p < 0.01) in fibrotic tissue. miRNA target prediction and overlap analysis indicated an interaction of the strongest deregulated miRNAs with 29 deregulated mRNAs. Pathway analysis revealed alterations in DNA repair, cell cycle regulation, and TGF-beta signaling. qRT-PCR confirmed differential expression of top deregulated miRNAs and mRNAs. CONCLUSIONS: In VUAS tissue, severe alterations on mRNA and miRNA level are found. These consistent changes give insights into the pathogenesis of VUAS after radical prostatectomy and point to future options for transcriptomics-based risk stratification and targeted therapies.

[True thymic hyperplasia : Differential diagnosis of thymic mass lesions in neonates and children]. / "Echte Thymushyperplasie" : Differenzialdiagnose der Thymusvergrößerung bei Säuglingen und Kindern.

Reactive and neoplastic thymic pathologies are the main considerations in the case of masses in the anterior and middle part of the mediastinum, while neurogenic tumors are predominant in the posterior mediastinum (which are not dealt with here). In neonates and infants, the commonest pathologies in the anterior mediastinum comprise germ cell tumors (mainly teratomas), congenital thymic cysts and true thymic hyperplasia (TTH). In toddlers, teratomas, yolk sac tumors and cysts predominate. In children over 5 years of age, lymphomas are the commonest mass lesions whereas thymomas and thymic carcinomas are rare. In addition, inflammation-linked hyperplasia in myasthenia gravis and rebound thymic hyperplasia after chemotherapy must be considered. Although rare at all ages, sarcomas must be considered in the differential diagnosis from birth onwards and throughout adolescence. Based on the report of a rare case of recurrent TTH, the differential diagnosis of this benign but potentially life-threatening condition is discussed.

[Thymomas]. / Thymome.

Thymomas are rare tumors but are one of the most common mediastinal neoplasms in adults and exhibit an enormous variability in histological, biological and genetic features. The morphological spectrum within a given entity is enormous and some tumors with histological patterns of more than one entity are more common than pure histological subtypes. Due to a lack of subtype-specific markers classification of thymomas often requires complex diagnostic algorithms. The refined presentation including the definition of obligatory and optional features and of diagnostic immunohistochemical profiles, is the focus of the new World Health Organization (WHO) classification of thymomas, aiming at improving diagnostic reproducibility. This review highlights novel aspects of the WHO classification of thymomas and addresses typical differential diagnostic challenges with a focus on diagnostic pitfalls.

[Thymic carcinomas]. / Thymuskarzinome.

Thymic carcinomas (TC) are approximately 10 times less prevalent than thymomas but of high clinical relevance because they are more aggressive, less frequently resectable than thymomas and usually refractory to classical and targeted long-term treatment approaches. Furthermore, in children and adolescents TC are more frequent than thymomas and particularly in this age group, germ cell tumors need to be a differential diagnostic consideration. In diagnostic terms pathologists face two challenges: a), the distinction between thymic carcinomas and thymomas with a similar appearance and b), the distinction between TC and histologically similar metastases and tumor extensions from other primary tumors. Overcoming these diagnostic challenges is the focus of the new WHO classification of thymic epithelial tumors. The objectives of this review are to highlight novel aspects of the WHO classification of thymic carcinomas and to address therapeutically relevant diagnostic pitfalls.

[Thymus cancers: A clinical observation]. / Thymustumoren : Eine klinische Betrachtung.

INTRODUCTION: Thymic tumors including thymomas, thymic carcinomas, and thymic carcinoid tumors are rare tumors with an incidence of 0.13/100,000. MATERIALS AND METHODS: A literature search was performed to identify recent findings on epidemiology, classification, and various therapeutic approaches. RESULTS: These tumors with a wide spectrum of histologic and biologic features may be clinically unapparent for a long time or show a very aggressive behavior with local invasion and distant metastases. Surgical resection is the mainstay in stage I and II thymomas, whereas in stage III thymomas and in thymomas with pleural dissemination surgery in context of a multimodal treatment should be discussed. Thymic tumors are chemoreactive. Targeted therapies show poor results and should only be considered in the palliative situation after failure of chemotherapy. CONCLUSION: The new TNM (T: tumor, N: node, M: metastasis) classification of thymic tumors will help to identify the best treatment options.