Oxygen supply maps for hypoxic microenvironment visualization in prostate cancer.

Background: Intratumoral hypoxia plays an important role with regard to tumor biology and susceptibility to radio- and chemotherapy. For further investigation of hypoxia-related changes, areas of certain hypoxia must be reliably detected within cancer tissues. Pimonidazole, a 2-nitroimindazole, accumulates in hypoxic tissue and can be easily visualized using immunohistochemistry.

PD-L1 expression is regulated by hypoxia inducible factor in clear cell renal cell carcinoma.

In our study, we demonstrate that ccRCC cell lines with impaired function of pVHL to degrade HIFα express elevated levels of PD-L1. In vitro analysis provided evidence that both reconstitution of pVHL and silencing of HIF2α, but not of HIF1α, lead to reduced PD-L1 expression. The strong correlation of expression between the HIF2α-specific HIF target Glut1 and PD-L1 confirmed this finding in ccRCC cell lines and tissue.

[Nephroblastomas: Almost exclusively in clinical trials!].

Nephroblastomas are the most commonly occurring renal neoplasms in childhood and are treated almost exclusively in clinical trials. An important factor for further therapeutic management is the pathological evaluation of the nephrectomy specimen. Tumor stage and risk group classification are the most crucial parameters.

[WHO classification 2016 and first S3 guidelines on renal cell cancer: What is important for the practice?].

The first S3 guidelines on renal cell cancer cover the practical aspects of imaging, diagnostics and therapy as well as the clinical relevance of pathology reporting. This review summarizes the changes in renal tumor classification and the new recommendations for reporting renal cell tumors. The S3 guidelines recommend the 2016 World Health Organization (WHO) classification of renal cell tumors.

The Value of In Vitro Diagnostic Testing in Medical Practice: A Status Report.

Background: In vitro diagnostic (IVD) investigations are indispensable for routine patient management. Appropriate testing allows early-stage interventions, reducing late-stage healthcare expenditure (HCE).

Aim: To investigate HCE on IVDs in two developed markets and to assess the perceived value of IVDs on clinical decision-making.

The IL-33/ST2 pathway contributes to intestinal tumorigenesis in humans and mice.

Colorectal cancer (CRC) develops through a multistep process and is modulated by inflammation. However, the inflammatory pathways that support intestinal tumors at different stages remain incompletely understood. Interleukin (IL)-33 signaling plays a role in intestinal inflammation, yet its contribution to the pathogenesis of CRC is unknown.

The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs-Part A: Renal, Penile, and Testicular Tumours.

Unlabelled: The fourth edition of the World Health Organization (WHO) classification of urogenital tumours (WHO "blue book"), published in 2016, contains significant revisions. These revisions were performed after consideration by a large international group of pathologists with special expertise in this area. A subgroup of these persons met at the WHO Consensus Conference in Zurich, Switzerland, in 2015 to finalize the revisions.

Clinical impact of prostate biopsy undergrading in an academic and community setting.

Purpose: To evaluate whether the rate of Gleason score (GS) upgrade on final pathology, the rate of positive surgical margins (PSM) and the rate of biochemical recurrence (BCR) after radical prostatectomy (RP) were different if prostate biopsy (PB) was graded by community pathologists (CP) as compared to specialized uro-pathologists (UP).

Methods: A consecutive series of patients undergoing RP in our institution between 2005 and 2013 were retrospectively reviewed. Any GS higher or lower in RP specimen as compared to PB GS was defined as GS upgrade or downgrade, respectively.

Homozygous G/G variant of SNP309 in the human MDM2 gene is associated with earlier tumor onset in Caucasian female renal cell carcinoma patients.

Human mouse double minute 2 (Mdm2) plays an essential role in the regulation of the tumor suppressor p53. The G/G variant of SNP309 was shown to increase Mdm2 mRNA/protein expression and to be associated with an increased risk and earlier onset of different cancers in Asian populations. However, the frequency and impact of these G/G variants have not been studied in Caucasian renal cell carcinoma (RCC) patients.

Cilengitide in newly diagnosed glioblastoma: biomarker expression and outcome.

Integrins αvβ3 and αvβ5 regulate angiogenesis and invasiveness in cancer, potentially by modulating activation of the transforming growth factor (TGF)-β pathway. The randomized phase III CENTRIC and phase II CORE trials explored the integrin inhibitor cilengitide in patients with newly diagnosed glioblastoma with versus without O6-methylguanine DNA methyltransferase (MGMT) promoter methylation. These trials failed to meet their primary endpoints.

Interleukin-33 Expression Indicates a Favorable Prognosis in Malignant Salivary Gland Tumors.

The cytokine interleukin-33 (IL-33) is abundantly expressed in epithelial barrier tissues such as salivary glands. Here, we characterized nuclear IL-33 protein expression by immunohistochemistry in benign and malignant salivary gland tumors and associated it with disease outcome. Most benign salivary gland tumors expressed IL-33, and all Warthin's tumors showed strong and consistent IL-33 expression in the basally oriented cells of their bilayered epithelium.

Emerging Immunotargets and Immunotherapies in Prostate Cancer.

Innate and adaptive immunity are both involved in prostate cancer (PCa) carcinogenesis and progression. On this scenario, several immunotherapeutic approaches have been proposed and are presently under extensive investigation in PCa patients. Among emerging immune targets, immune checkpoint inhibitors such as anti-cytotoxic T-lymphocyteassociated protein 4 (CTLA-4), anti-Programmed death-1 (PD-1) and anti-Programmed death-ligand-1 (PD-L1) agents seem to represent the most promising candidate for these patients, together with oncolytic viruses and vaccines, used alone or in combined strategies.

Prognostic relevance of lactate dehydrogenase and serum S100 levels in stage IV melanoma with known BRAF mutation status.

Background: Activating mutations of BRAF provide an important treatment target in patients with melanoma. The prognostic role of several biochemical markers in relation to mutation status is not clear.

Objectives: To analyse the prognostic significance of BRAF mutation in patients with melanoma and correlate it to different markers.

An Overview of Emerging Immunotargets of Genitourinary Tumors.

Emerging immunotherapies targeting immune checkpoints and tumor associated antigens are leading to important clinical advances and providing a new weapon in patients with prostate (PCa) and bladder cancer (BC) and, in particular, with renal cell carcinoma (RCC). The possibility to integrate these agents in the current therapeutic scenario or genitourinary tumors, both in sequential or combined approaches, relies on a more profound comprehension of the protumorigenic activity of the immune system and of the mechanisms of cancer-related immunosuppression. In this regards, neutrophils, T and B lymphocytes and tumor-associated macrophages (TAMs) are implicated in the pathogenesis, progression and development of drug resistance in genitourinary tumors.

Interaction of tumor cells with infiltrating lymphocytes via CD70 and CD27 in clear cell renal cell carcinoma.

CD70 upregulation by hypoxia-inducible factor and CD27 lymphocyte tumor infiltration are associated with worse survival in von Hippel-Lindau gene mutated clear cell renal cell carcinoma (ccRCC). CD70/CD27 interaction is accompanied by high soluble CD27 levels in the sera of ccRCC patients suggesting that soluble CD27 is a potential predictive tool for anti-CD70 therapy.

[Leiomyomatous renal cell carcinoma : Controversy around a new entity].

While clear cell, papillary and chromophobic renal cell carinoma (RCC) represent the most common malignant renal neoplasms, the evaluation and classification of rare renal carcinomas has currently come into focus. One of these is the leiomyomatous RCC, which shows morphologic similarities to clear cell RCCs, however exhibiting additional, atypical smooth muscle differentiation. We report the clinical case of a patient simultaneously presenting with leiomyomatous and papillary RCC and discuss new tumor entities of RCC.

A novel pVHL-independent but NEMO-driven pathway in renal cancer promotes HIF stabilization.

Activation of hypoxia-inducible factor (HIF) is due to loss of von Hippel-Lindau protein (pVHL) function in most clear cell renal cell carcinomas (ccRCCs). Here we describe a novel pVHL-independent mechanism of HIF regulation and identify nuclear factor (NF)-κB essential modulator (NEMO) as a hitherto unknown oncogenic factor influencing human ccRCC progression. Over 60% of human ccRCCs (n=157) have negative or weak NEMO protein expression by immunohistochemistry.

Analysis of BRAF and NRAS Mutation Status in Advanced Melanoma Patients Treated with Anti-CTLA-4 Antibodies: Association with Overall Survival?

Ipilimumab and tremelimumab are human monoclonal antibodies (Abs) against cytotoxic T-lymphocyte antigen-4 (CTLA-4). Ipilimumab was the first agent to show a statistically significant benefit in overall survival in advanced melanoma patients. Currently, there is no proven association between the BRAFV600 mutation and the disease control rate in response to ipilimumab.

Brain metastases in gastro-oesophageal adenocarcinoma: insights into the role of the human epidermal growth factor receptor 2 (HER2).

Background: Gastro-oesophageal adenocarcinomas rarely metastasize to the central nervous system (CNS). The role of the human epidermal growth factor receptor 2 (HER2) in patients with these cancers and CNS involvement is presently unknown.

Patients And Methods: A multicentre registry was established to collect data from patients with gastro-oesophageal adenocarcinomas and CNS involvement both retrospectively and prospectively.

Hypoxia, Hypoxia-inducible Transcription Factors, and Renal Cancer.

Context: Renal cancer is a common urologic malignancy, and therapeutic options for metastatic disease are limited. Most clear cell renal cell carcinomas (ccRCC) are associated with loss of von Hippel-Lindau tumor suppressor (pVHL) function and deregulation of hypoxia pathways.

Objective: This review summarizes recent evidence from genetic and biological studies showing that hypoxia and hypoxia-related pathways play critical roles in the development and progress of renal cancer.

Connexin 43 expression predicts poor progression-free survival in patients with non-muscle invasive urothelial bladder cancer.

Objectives: To evaluate the protein expression of connexin 43 (Cx43) in primary urothelial bladder cancer and test its association with the histopathological characteristics and clinical outcome.

Methods: A tissue microarray containing 348 tissue samples from 174 patients with primary urothelial carcinomas of the bladder was immunohistochemically stained for Cx43. The intensity of staining was semiquantitatively evaluated (score 0, 1+, 2+), and the association with clinicopathological features was assessed.