No abstract

There are several U.S. FDA-cleared molecular respiratory virus panels available today, each with advantages and disadvantages. This study compares four multiplex panels, the BioFire Diagnostics FilmArray RP (respiratory panel), the GenMark Dx eSensor RVP (respiratory viral panel), the Luminex xTAG RVPv1, and the Luminex xTAG RVP fast. Three hundred specimens (200 retrospective and 100 consecutive) were tested using all four platforms to determine performance characteristics. The overall sensitivity and specificity, respectively, and 95% confidence interval (CI; in parentheses) for each panel were as follows: FilmArray RP, 84.5% (

© F e r r a t a S t o r t i F o u n d a t i o nBCL2 translocations are more frequently found in the GCB subtype, whereas 18q21 locus amplification is more common in the ABC subtype of DLBCL. 3,8,10 The prognostic significance of BCL2 amplification or translocations in de novo DLBCL in the era of CHOP therapy alone, without rituximab, was controversial. [11][12][13][14][15][16][17][18][19][20] Some data on the prognostic significance of BCL2 aberrations in patients treated with R-CHOP have recently become available, with two studies reporting no influence of BCL2 gene rearrangements on the survival of DLBCL patients. 21,22 On the other hand, the concomitant presence of t(14;18) or variants and MYC rearrangements, referred to as double hit lymphomas, has consistently been associated with adverse outcome in DLBCL patients treated with R-CHOP. [23][24][25] Bcl-2 protein expression seems only partially related to BCL2 gene abnormalities as analyzed by fluorescence in situ hybridization (FISH), as Bcl-2 is expressed in a greater number of DLBCL cases than in those tumors carrying t(14;18)(q32;q21). [10][11][12] Indeed, in the absence of BCL2 translocations, amplification of 18q21 and/or activation of the nuclear factor κB (NF-κB) pathway can cause Bcl-2 protein overexpression. 26 The prognostic significance of Bcl-2 expression is also controversial, and comparison between different studies is hampered by the choice of different cut-offs of positive cells, and by the variability of treatments. In patients treated with R-CHOP, Bcl-2 protein did not correlate with outcome, 5,27 since the addition of rituximab seemed to improve survival of Bcl-2-positive patients, [28][29][30] apparently eliminating the gap between Bcl-2-positive and Bcl-2-negative patients found in the pre-rituximab era. This result does, however, appear to be contradicted in a very recent study in which Bcl-2 expression in GCB-DLBCL was associated with poorer outcome. 22 The goal of this study was to investigate the prognostic value of BCL2 gene aberrations and Bcl-2 expression in a large number of patients with de novo DLBCL, uniformly treated with R-CHOP, for whom MYC and GEP characterization was available. Design and Methods PatientsWe studied 327 cases of previously untreated de novo DLBCL, diagnosed between January 2002 and October 2009, and collected as part of the International DLBCL Rituxan-CHOP Consortium Program Study. These cases were analyzed for Bcl-2 protein expression, and BCL2 and MYC gene abnormalities, and gene expression profiling (GEP) was performed. All cases were reviewed by a group of hematopathologists (SMM, MAP, MBM, AT, and KHY), and the diagnoses were confirmed based on World Health Organization classification criteria. Patients with transformation from low grade lymphoma, those with composite follicular lymphoma, primary mediastinal large B-cell lymphoma, primary cutaneous and primary central nervous system DLBCL were excluded from the analysis due to the unique biological features of these types of lymphoma. All pat...

Tumor‐infiltrating myeloid cells are the most abundant leukocyte population within tumors. Molecular cues from the tumor microenvironment promote the differentiation of immature myeloid cells toward an immunosuppressive phenotype. However, the in situ dynamics of the transcriptional reprogramming underlying this process are poorly understood. Therefore, we applied single cell RNA‐seq (scRNA‐seq) to computationally investigate the cellular composition and transcriptional dynamics of tumor and adjacent normal tissues from 4 early‐stage non‐small cell lung cancer (NSCLC) patients. Our scRNA‐seq analyses identified 11 485 cells that varied in identity and gene expression traits between normal and tumor tissues. Among these, myeloid cell populations exhibited the most diverse changes between tumor and normal tissues, consistent with tumor‐mediated reprogramming. Through trajectory analysis, we identified a differentiation path from CD14+ monocytes to M2 macrophages (monocyte‐to‐M2). This differentiation path was reproducible across patients, accompanied by increased expression of genes (eg, MRC1/CD206, MSR1/CD204, PPARG, TREM2) with significantly enriched functions (Oxidative phosphorylation and P53 pathway) and decreased expression of genes (eg, CXCL2, IL1B) with significantly enriched functions (TNF‐α signaling via NF‐κB and inflammatory response). Our analysis further identified a co‐regulatory network implicating upstream transcription factors (JUN, NFKBIA) in monocyte‐to‐M2 differentiation, and activated ligand‐receptor interactions (eg, SFTPA1‐TLR2, ICAM1‐ITGAM) suggesting intratumoral mechanisms whereby epithelial cells stimulate monocyte‐to‐M2 differentiation. Overall, our study identified the prevalent monocyte‐to‐M2 differentiation in NSCLC, accompanied by an intricate transcriptional reprogramming mediated by specific transcriptional activators and intercellular crosstalk involving ligand‐receptor interactions.

Tissue biopsy is the standard diagnostic procedure for cancer. Biopsy may also provide material for genotyping, which can assist in the diagnosis and selection of targeted therapies but may fall short in cases of inadequate sampling, particularly from highly heterogeneous tumors. Traditional tissue biopsy suffers greater limitations in its prognostic capability over the course of disease, most obviously as an invasive procedure with potential complications, but also with respect to probable tumor clonal evolution and metastasis over time from initial biopsy evaluation. Recent work highlights circulating tumor DNA (ctDNA) present in the blood as a supplemental, or perhaps an alternative, source of DNA to identify the clinically relevant cancer mutational landscape. Indeed, this noninvasive approach may facilitate repeated monitoring of disease progression and treatment response, serving as a means to guide targeted therapies based on detected actionable mutations in patients with advanced or metastatic solid tumors. Notably, ctDNA is heralding a revolution in the range of genomic profiling and molecular mechanisms to be utilized in the battle against cancer. This review will discuss the biology of ctDNA, current methods of detection and potential applications of this information in tumor diagnosis, treatment, and disease prognosis. Conventional classification of tumors to describe cancer stage follow the TNM notation system, heavily weighting local tumor extent (T), lymph node invasion (N), and detectable metastasis (M). With recent advancements in genomics and bioinformatics, it is conceivable that routine analysis of ctDNA from liquid biopsy (B) may make cancer diagnosis, treatment, and prognosis more accurate for individual patients. We put forward the futuristic concept of TNMB tumor classification, opening a new horizon for precision medicine with the hope of creating better outcomes for cancer patients.

No abstract

Mutations in polymerase ε (POLE) confer favorable prognosis and outcomes in various cancer types, but their role in non-small cell lung cancer (NSCLC) is unknown. Utilizing the data of 513 patients with adenocarcinoma (LUAD) and 497 patients with squamous cell carcinoma (LUSC) from The Cancer Genome Atlas (TCGA) cohort, we tested the prognostic value of POLE mutations and programmed cell death ligand 1 (PD-L1) expression in the two main subtypes of NSCLC. POLE mutation is a favorable biomarker for the improved overall survival (OS) of the LUSC patients (P = 0.033, 28 mutant vs. 469 wildtype patients), but not that of the LUAD patients (P = 0.12, 31 mutant vs. 482 wildtype patients). POLE-mutant LUAD patients with high expression of PD-L1 (Mut-High, n = 6) exhibited improved OS (P = 0.024) when compared to POLE-mutant patients with low PD-L1 expression (Mut-Low, n = 24) and other patients without POLE mutation (n = 476). This benefit was not due to the high content of the tumor infiltrating lymphocytes. Instead, the antitumor immune response was activated in Mut-High patients so that these patients were likely responding more effectively to immuno-oncology (IO) treatments; whereas genes involved with metabolic pathways were enriched in Mut-Low group, which may cause the decreased OS of these patients. Our study sheds light on the molecular basis of NSCLC and adds to our understanding of responses to chemotherapy and IO therapy.Electronic supplementary materialThe online version of this article (10.1186/s12943-018-0832-y) contains supplementary material, which is available to authorized users.

Although idiopathic hypereosinophilic syndrome (HES) is uncommon, we studied the clinical characteristics of this disorder in patients with cutaneous involvement. We chronicle the case of a patient with diffuse skin rash due to idiopathic HES from our clinical experience. Furthermore, a systematic literature search of the medical databases PubMed and Google Scholar was conducted. A total of 32 cases fulfilled the inclusion criteria. The data on patients’ characteristics, epidemiology, clinical features, diagnosis, treatment and outcome were collected and analysed. This review illustrates that physicians should maintain a high index of clinical suspicion for idiopathic HES in patients presenting with dermatological lesions and hypereosinophilia, without an obvious cause. Randomised clinical trials are warranted to outline a generalised and efficient therapeutic approach in these patients. Additionally, this paper highlights the need for population-based studies to delineate the magnitude and scope of this association.