Identification of high-risk patients with a seven-biomarker prognostic signature for adjuvant treatment trial recruitment in American Joint Committee on Cancer v8 stage I-IIA cutaneous melanoma.

Purpose: Many patients with resected American Joint Committee on Cancer (AJCC) early-stage cutaneous melanoma nonetheless die of melanoma; additional risk stratification approaches are needed.

Patients And Methods: Using prospectively-collected whole-tissue sections, we assessed in consecutive stage I-IIA patients (N = 439), a previously-validated, immunohistochemistry-based, 7-biomarker signature to prognosticate disease-free survival (DFS), melanoma-specific survival (MSS; primary end-point) and overall survival (OS), independent of AJCC classification.

Results: Seven-marker signature testing designated 25.

Modified immunoscore improves the prediction of progression-free survival in patients with non-muscle-invasive bladder cancer: A digital pathology study.

Tumour-infiltrating lymphocytes (TIL), known to be of prognostic value in various solid tumours, have been in the focus of research in the last years. TIL are often quantified IMMUNOSCORE (IS), a scoring system based on TIL cell densities. Recent studies were able to replicate these findings for muscle-invasive bladder cancer (MIBC), however data regarding non-muscle-invasive bladder cancer (NMIBC) are scarce.

Modified Immunoscore Improves Prediction of Survival Outcomes in Patients Undergoing Radical Cystectomy for Bladder Cancer-A Retrospective Digital Pathology Study.

To evaluate the prognostic value of a modified Immunoscore (mIS) in a cohort of bladder cancer (BC) patients undergoing radical cystectomy (RC), two tissue microarrays of 159 BC patients were immunohistochemically stained for CD3/CD8/FOXP3 and CD45RO to detect Tumor-Infiltrating Lymphocytes (TIL). To predict progression free survival (PFS) and cancer specific survival (CSS), a predictive model cumulatively incorporating all four components was constructed and labeled as mIS. Patients were stratified into two risk groups; "high mIS/favorable risk" and "low mIS/unfavorable risk".

Characterization of Tumor Blood Vasculature Expression of Human Invasive Bladder Cancer by Laser Capture Microdissection and Transcriptional Profiling.

Tumor-associated blood vessels differ from normal vessels and play key roles in tumor progression. We aimed to identify biomolecules that are expressed differentially in human bladder cancer-associated blood vessels to find novel biomarkers and mechanisms involved in tumor-associated angiogenesis. The transcriptome of tumor blood vasculature from human invasive bladder carcinoma (I-BLCA) and normal bladder tissue vasculature was compared using differential expression and unsupervised hierarchical clustering analyses.

Multicenter Validation of Histopathologic Tumor Regression Grade After Neoadjuvant Chemotherapy in Muscle-invasive Bladder Carcinoma.

Response classification after neoadjuvant chemotherapy in muscle-invasive bladder carcinoma is based on the TNM stage at radical cystectomy. We recently showed that histopathologic tumor regression grades (TRGs) add prognostic information to TNM. Our aim was to validate the prognostic significance of TRG in muscle-invasive bladder cancer in a multicenter setting.

BioScore (B7-H1, survivin, and Ki-67) does not predict cancer-specific mortality in surgically treated patients with renal cell carcinoma: An external validation study.

Background: To externally validate' BioScore', a biomarker-based scoring system using immunohistochemical tumor expression levels of B7-H1, survivin, and Ki-67, in a single-center cohort of renal cell carcinoma (RCC) patients. Additionally, we investigated the potential benefit of BioScore as compared to the Mayo Clinic stage, size, grade, and necrosis (SSIGN) score.

Materials And Methods: The validation cohort comprised 393 nonmetastatic RCC patients treated with radical nephrectomy or nephron-sparing surgery from 1999 to 2004.

[CME: Acquired Hemophagocytic Lymphohistiocytosis].

CME: Acquired Hemophagocytic Lymphohistiocytosis Abstract. Acquired hemophagocytic lymphohistiocytosis comprises a heterogenous group of hyperinflammatory immunoreactions often resulting in uncontrolled immune responses, mainly throughout proliferation of cytotoxic T cells and hemophagocytosis by macrophages. Hemophagocytic lymphohistiocytosis is often underdiagnosed, contributing to its high morbidity and mortality.

Author Correction: Aberrant methylated key genes of methyl group metabolism within the molecular etiology of urothelial carcinogenesis.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Aberrant methylated key genes of methyl group metabolism within the molecular etiology of urothelial carcinogenesis.

Urothelial carcinoma (UC), the most common cancer of the urinary bladder causes severe morbidity and mortality, e.g. about 40.

p53-expression in patients with renal cell carcinoma correlates with a higher probability of disease progression and increased cancer-specific mortality after surgery but does not enhance the predictive accuracy of robust outcome models.

Objective: Due to lacking external validation, molecular biomarkers are currently not applied for risk-stratification of patients with localized renal cell carcinoma. The objective of this study was to externally validate a molecular multi-marker panel included in a previously proposed prognostic nomogram for the prediction of postoperative disease-free survival.

Methods And Materials: Besides pathologic tumor stage (pT) and ECOG-Performance Status, the nomogram includes 5 molecular markers (Ki-67, p53, VEGFR-1 endothelial or epithelial, and VEGF-D epithelial).

Prostate cancer-associated SPOP mutations confer resistance to BET inhibitors through stabilization of BRD4.

The bromodomain and extraterminal (BET) family of proteins comprises four members-BRD2, BRD3, BRD4 and the testis-specific isoform BRDT-that largely function as transcriptional coactivators and play critical roles in various cellular processes, including the cell cycle, apoptosis, migration and invasion. BET proteins enhance the oncogenic functions of major cancer drivers by elevating the expression of these drivers, such as c-Myc in leukemia, or by promoting the transcriptional activities of oncogenic factors, such as AR and ERG in prostate cancer. Pathologically, BET proteins are frequently overexpressed and are clinically linked to various types of human cancer; they are therefore being pursued as attractive therapeutic targets for selective inhibition in patients with cancer.

High expression of insulin receptor on tumour-associated blood vessels in invasive bladder cancer predicts poor overall and progression-free survival.

Bladder cancer is a frequently recurring disease with a very poor prognosis once progressed to invasive stages, and tumour-associated blood vessels play a crucial role in this process. In order to identify novel biomarkers associated with progression, we isolated blood vascular endothelial cells (BECs) from human invasive bladder cancers and matched normal bladder tissue, and found that tumour-associated BECs greatly up-regulated the expression of insulin receptor (INSR). High expression of INSR on BECs of invasive bladder cancers was significantly associated with shorter progression-free and overall survival.

Iris cyst in a child with Aicardi syndrome: a novel association.

Aicardi syndrome is a rare X-linked cerebro-retinal disorder characterized by agenesis or dysgenesis of the corpus callosum, seizures, and chorioretinal lacunae; microphthalmia or optic nerve coloboma may also be observed. We report the case of an infant born with severe ocular malformations, including an anterior chamber cyst in one eye, which was surgically removed.

CD73 Predicts Favorable Prognosis in Patients with Nonmuscle-Invasive Urothelial Bladder Cancer.

Aims: CD73 is a membrane associated 5'-ectonucleotidase that has been proposed as prognostic biomarker in various solid tumors. The aim of this study is to evaluate CD73 expression in a cohort of patients with primary bladder cancer in regard to its association with clinicopathological features and disease course.

Methods: Tissue samples from 174 patients with a primary urothelial carcinoma were immunohistochemically assessed on a tissue microarray.

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.

Diagnostic Accuracy of Quantitative and Qualitative Phase-Contrast Imaging for the ex Vivo Characterization of Human Coronary Atherosclerotic Plaques.

Purpose: To investigate the accuracy of x-ray grating interferometry phase-contrast (PC) imaging for the characterization of human coronary artery plaque.

Materials And Methods: PC and conventional absorption computed tomographic (CT) imaging was performed ex vivo in this institutional review board-approved study in 40 human coronary artery segments by using a synchrotron radiation source. Qualitative analyses and calculations of image quality (McNemar test), plaque components (McNemar test), and plaque classification (Cohen κ test) according to the American Heart Association classification were performed in 38 plaques detected at histopathologic examination (reference standard).

Unique composite hematolymphoid tumor consisting of a pro-T lymphoblastic lymphoma and an indeterminate dendritic cell tumor: evidence for divergent common progenitor cell differentiation.

Until recently, hematopoietic neoplasms were considered monoclonal proliferations belonging to one cell lineage. In the last years, evidence for transdifferentiation from one cell lineage to another or divergent common progenitor cell differentiation has accumulated, mainly based on composite hematolymphoid tumors, sharing common genetic abnormalities. We report the case of a 59-year-old woman with a composite pro-T lymphoblastic lymphoma (LBL) and indeterminate dendritic cell tumor infiltrating the lymph nodes, bone marrow and stomach.

Midregional pro-adrenomedullin in addition to b-type natriuretic peptides in the risk stratification of patients with acute dyspnea: an observational study.

Introduction: The identification of patients at highest risk for adverse outcome who are presenting with acute dyspnea to the emergency department remains a challenge. This study investigates the prognostic value of the newly described midregional fragment of the pro-Adrenomedullin molecule (MR-proADM) alone and combined to B-type natriuretic peptide (BNP) or N-terminal proBNP (NT-proBNP) in patients with acute dyspnea.

Methods: We conducted a prospective, observational cohort study in the emergency department of a University Hospital and enrolled 287 unselected, consecutive patients (48% women, median age 77 (range 68 to 83) years) with acute dyspnea.