Multiplatform molecular test performance in indeterminate thyroid nodules.

Background: Approximately 25% of thyroid nodule fine-needle aspirates (FNAs) have cytology that is indeterminate for malignant disease. Accurate risk stratification of these FNAs with ancillary testing would reduce unnecessary thyroid surgery.

Methods: We evaluated the performance of an ancillary multiplatform test (MPTX) that has three diagnostic categories (negative, moderate, and positive).

Incremental value of DNA analysis in pancreatic cysts stratified by clinical risk factors.

Background And Aims: We determined the incremental predictive value of pancreatic cyst fluid molecular analysis to assessing malignancy risk over long-term follow-up of a well-characterized cohort, given the underlying predictive value of imaging parameters routinely used to triage such patients.

Methods: Patients who lacked initial cytologic malignancy in cyst fluid and had final pathology or a follow-up period of more than 2 years were included. Patient outcomes determined the malignancy-free survival of patients with high-risk stigmata (HRS), worrisome features (WFs), and DNA abnormalities.

The Diagnostic Yield of Malignancy Comparing Cytology, FISH, and Molecular Analysis of Cell Free Cytology Brush Supernatant in Patients With Biliary Strictures Undergoing Endoscopic Retrograde Cholangiography (ERC): A Prospective Study.

Background: Routine cytology of biliary stricture brushings obtained during endoscopic retrograde cholangiopancreatography (ERCP) has suboptimal sensitivity for malignancy. We compared the individual and combined ability of cytology, fluorescence in situ hybridization (FISH) analysis and PCR-based mutation profiling (MP) to detect malignancy in standard biliary brushings.

Methods: We performed a prospective study of patients undergoing ERCP using histology or 1 year follow-up to determine patient outcomes.

Mutation Profile and Fluorescence In Situ Hybridization Analyses Increase Detection of Malignancies in Biliary Strictures.

Background & Aims: It is a challenge to detect malignancies in biliary strictures. Various sampling methods are available to increase diagnostic yield, but these require additional procedure time and expertise. We evaluated the combined accuracy of fluorescence in situ hybridization (FISH) and polymerase chain reaction-based DNA mutation profiling (MP) of specimens collected using standard brush techniques.

Endoscopic ablation is a cost-effective cancer preventative therapy in patients with Barrett's esophagus who have elevated genomic instability.

Background: The surveillance of patients with nondysplastic Barrett's esophagus (NDBE) has a high cost and is of limited effectiveness in preventing esophageal adenocarcinoma (EAC). Ablation for NDBE remains expensive and controversial. Biomarkers of genomic instability have shown promise in identifying patients with NDBE at high risk for progression to EAC.

The Presence of Genetic Mutations at Key Loci Predicts Progression to Esophageal Adenocarcinoma in Barrett's Esophagus.

Objectives: Risk stratification in Barrett's esophagus (BE) is challenging. We evaluated the ability of a panel of genetic markers to predict progression to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC).

Methods: In this case-control study, we assessed a measure of genetic instability, the mutational load (ML), in predicting progression to HGD or EAC.

The added value of using mutational profiling in addition to cytology in diagnosing aggressive pancreaticobiliary disease: review of clinical cases at a single center.

Background: This study aimed to better understand the supporting role that mutational profiling (MP) of DNA from microdissected cytology slides and supernatant specimens may play in the diagnosis of malignancy in fine-needle aspirates (FNA) and biliary brushing specimens from patients with pancreaticobiliary masses.

Methods: Cytology results were examined in a total of 30 patients with associated surgical (10) or clinical (20) outcomes. MP of DNA from microdissected cytology slides and from discarded supernatant fluid was analyzed in 26 patients with atypical, negative or indeterminate cytology.

Assessment of mutational load in biopsy tissue provides additional information about genomic instability to histological classifications of Barrett's esophagus.

Purpose: Progression of Barrett's esophagus (BE) to esophageal adenocarcinoma (EAC) is associated with accumulated genomic instability. Current risk stratification of BE for EAC relies on histological classification and grade of dysplasia. However, histology alone cannot assess the risk of patients with inconsistent or non-dysplastic BE histology.

The value of mutational profiling of the cytocentrifugation supernatant fluid from fine-needle aspiration of pancreatic solid mass lesions.

Fine-needle aspiration (FNA) of pancreatic solid masses can be significantly impacted by sampling variation. Molecular analysis of tumor DNA can be an aid for more definitive diagnosis. The aim of this study was to evaluate how molecular analysis of the cell-free cytocentrifugation supernatant DNA can help reduce sampling variability and increase diagnostic yield.

Correlation of the presence and extent of loss of heterozygosity mutations with histological classifications of Barrett's esophagus.

Background: Recent advances in the management of Barrett's Esophagus (BE) have placed greater emphasis on accurate diagnosis of BE as well as better prediction of risk for progression to esophageal adenocarcinoma (EAC). Histological evaluation of BE is particularly challenging with significant inter-observer variability. We explored the presence and extent of genomic instability in BE biopsy specimens as a means to add supplementary information to the histological classification and clinical decision-making related to early disease.

Phosphorylation of the varicella-zoster virus (VZV) major transcriptional regulatory protein IE62 by the VZV open reading frame 66 protein kinase.

IE62, the major transcriptional regulatory protein encoded by varicella-zoster virus (VZV), is nuclear at early times of VZV infection but then becomes predominantly cytoplasmic as a result of expression of the protein kinase encoded by open reading frame 66 (ORF66). Cytoplasmic forms of IE62 are required for its inclusion as an abundant VZV virion tegument protein. Here we show that ORF66 directly phosphorylates IE62 at two residues, with phosphorylation at S686 being sufficient to regulate IE62 nuclear import.

Relationship of herpes simplex virus genome configuration to productive and persistent infections.

Infection of susceptible cells by herpes simplex virus (HSV) can lead to productive infection or to latency, where the genomes persist in the nuclei of peripheral neurons in a quiescent state. Using the HSV strain d109, which does not express any viral genes and thus establishes a quiescent state in most cells, we observed that a fraction of genomes circularized upon infection. The expression of infected cell protein (ICP) 0, which is known to be involved in reactivation from latency and the promotion of productive infection, inhibited the formation of circular genomes.