Analysis of laboratory data transmission between two healthcare institutions using a widely used point-to-point health information exchange platform: a case report.

Objective: The objective was to identify information loss that could affect clinical care in laboratory data transmission between 2 health care institutions via a Health Information Exchange platform.

Materials And Methods: Data transmission results of 9 laboratory tests, including LOINC codes, were compared in the following: between sending and receiving electronic health record (EHR) systems, the individual Health Level Seven International (HL7) Version 2 messages across the instrument, laboratory information system, and sending EHR.

Results: Loss of information for similar tests indicated the following potential patient safety issues: (1) consistently missing specimen source; (2) lack of reporting of analytical technique or instrument platform; (3) inconsistent units and reference ranges; (4) discordant LOINC code use; and (5) increased complexity with multiple HL7 versions.

Principles of Analytic Validation of Immunohistochemical Assays: Guideline Update.

Context.—: In 2014, the College of American Pathologists developed an evidence-based guideline to address analytic validation of immunohistochemical assays. Fourteen recommendations were offered.

Utility of Whole Slide Imaging for Intraoperative Consultation: Experience of a Large Academic Center.

Context.—: In the United States, review of digital whole slide images (WSIs) using specific systems is approved for primary diagnosis but has not been implemented for intraoperative consultation.

Objective.

MicroRNA-17 acts as a tumor chemosensitizer by targeting JAB1/CSN5 in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is the breast cancer subtype with the poorest prognosis. Evidence indicates that aberrant JAB1/CSN5 expression is associated with advanced tumor stage and poor prognosis in breast cancer. In this study, we evaluated expression of JAB1 in TNBC and potential mechanisms regulating this expression.

Multiclonal Invasion in Breast Tumors Identified by Topographic Single Cell Sequencing.

Ductal carcinoma in situ (DCIS) is an early-stage breast cancer that infrequently progresses to invasive ductal carcinoma (IDC). Genomic evolution has been difficult to delineate during invasion due to intratumor heterogeneity and the low number of tumor cells in the ducts. To overcome these challenges, we developed Topographic Single Cell Sequencing (TSCS) to measure genomic copy number profiles of single tumor cells while preserving their spatial context in tissue sections.

DCIS Margins and Breast Conservation: MD Anderson Cancer Center Multidisciplinary Practice Guidelines and Outcomes.

Recent published guidelines suggest that adequate margins for DCIS should be ≥ 2 mm after breast conserving surgery followed by radiotherapy (RT). Many groups now use this guideline as an absolute indication for additional surgery. This article describes detailed multidisciplinary practices including extensive preoperative/intraoperative pathologic/histologic image-guided assessment of margins, offering some patients with small low/intermediate grade DCIS no RT, the use/magnitude of radiation boost tailoring to margin width, and endocrine therapy for ER-positive DCIS.

2013 HIPAA Changes Provide Opportunities and Challenges for Researchers: Perspectives from a Cancer Center.

In 2013, the U.S. Department of Health and Human Services modified the Health Insurance Portability and Accountability Act Privacy Rule to "strengthen privacy and security protections" while "improving workability and effectiveness to increase flexibility for and decrease burden on regulated entities.

The Pan-Cancer analysis of pseudogene expression reveals biologically and clinically relevant tumour subtypes.

Although individual pseudogenes have been implicated in tumour biology, the biomedical significance and clinical relevance of pseudogene expression have not been assessed in a systematic way. Here we generate pseudogene expression profiles in 2,808 patient samples of seven cancer types from The Cancer Genome Atlas RNA-seq data using a newly developed computational pipeline. Supervised analysis reveals a significant number of pseudogenes differentially expressed among established tumour subtypes and pseudogene expression alone can accurately classify the major histological subtypes of endometrial cancer.

Challenges of the information age: the impact of false discovery on pathway identification.

Background: Pathways with members that have known relevance to a disease are used to support hypotheses generated from analyses of gene expression and proteomic studies. Using cancer as an example, the pitfalls of searching pathways databases as support for genes and proteins that could represent false discoveries are explored.

Findings: The frequency with which networks could be generated from 100 instances each of randomly selected five and ten genes sets as input to MetaCore, a commercial pathways database, was measured.

Patient-calibrated agent-based modelling of ductal carcinoma in situ (DCIS): from microscopic measurements to macroscopic predictions of clinical progression.

Ductal carcinoma in situ (DCIS)--a significant precursor to invasive breast cancer--is typically diagnosed as microcalcifications in mammograms. However, the effective use of mammograms and other patient data to plan treatment has been restricted by our limited understanding of DCIS growth and calcification. We develop a mechanistic, agent-based cell model and apply it to DCIS.

Metastatic neuroendocrine tumour in the breast: a potential mimic of in-situ and invasive mammary carcinoma.

Aims: The aim of this study was to review the clinicopathological characteristics of neuroendocrine tumours (NETs) metastasizing to the breast, in order to identify features that could be useful in distinguishing these metastatic lesions from primary breast neoplasms.

Methods And Results: Eighteen metastatic NETs in the breast were identified from two large hospitals over a 15-year period. Eleven (62%) tumours originated in the gastrointestinal tract, 5 (28%) originated in the lung, and the other two were of indeterminate origin.

A novel, patient-specific mathematical pathology approach for assessment of surgical volume: application to ductal carcinoma in situ of the breast.

We introduce a novel "mathematical pathology" approach, founded on a biophysical model, to identify robust patient-specific predictors of tumor growth useful in clinical practice to improve the accuracy of diagnosis/prognosis and intervention. In accordance with biological observations, our model simulates the diffusion-limited in situ tumors with a relatively short phase of fast initial growth, followed by a prolonged slow-growth phase where tumor size is constrained primarily by the relative weight of cell mitosis and death. The former phase may only last for a few months, so that at the time of diagnosis, we may assume that most tumors will have entered the phase where their size is changing slowly.

Selective genomic copy number imbalances and probability of recurrence in early-stage breast cancer.

A number of studies of copy number imbalances (CNIs) in breast tumors support associations between individual CNIs and patient outcomes. However, no pattern or signature of CNIs has emerged for clinical use. We determined copy number (CN) gains and losses using high-density molecular inversion probe (MIP) arrays for 971 stage I/II breast tumors and applied a boosting strategy to fit hazards models for CN and recurrence, treating chromosomal segments in a dose-specific fashion (-1 [loss], 0 [no change] and +1 [gain]).

Multiplicity: an organizing principle for cancers and somatic mutations.

Background: With the advent of whole-genome analysis for profiling tumor tissue, a pressing need has emerged for principled methods of organizing the large amounts of resulting genomic information. We propose the concept of multiplicity measures on cancer and gene networks to organize the information in a clinically meaningful manner. Multiplicity applied in this context extends Fearon and Vogelstein's multi-hit genetic model of colorectal carcinoma across multiple cancers.

Bagged gene shaving for the robust clustering of high-throughput data.

The analysis of high-throughput data sets, such as microarray data, often requires that individual variables (genes, for example) be grouped into clusters of variables with highly correlated values across all samples. Gene shaving is an established method for generating such clusters, but is overly sensitive to the input data: changing just one sample can determine whether or not an entire cluster is found. This paper describes a clustering method based on the bootstrap aggregation of gene shaving clusters, which overcomes this and other problems, and applies the new method to a large gene expression microarray dataset from brain tumour samples.

The deployment of a tissue request tracking system for the CHTN: a case study in managing change in informatics for biobanking operations.

Background: Managing change has not only been recognized as an important topic in medical informatics, but it has become increasingly important in translational informatics. The move to share data, together with the increasing complexity and volume of the data, has precipitated a transition from locally stored worksheet and flat files to relational data bases with object oriented interfaces for data storage and retrieval. While the transition from simple to complex data structures, mirroring the transition from simple to complex experimental technologies, seems natural, the human factor often fails to be adequately addressed leading to failures in managing change.

Gene expression meta-analysis supports existence of molecular apocrine breast cancer with a role for androgen receptor and implies interactions with ErbB family.

Background: Pathway discovery from gene expression data can provide important insight into the relationship between signaling networks and cancer biology. Oncogenic signaling pathways are commonly inferred by comparison with signatures derived from cell lines. We use the Molecular Apocrine subtype of breast cancer to demonstrate our ability to infer pathways directly from patients' gene expression data with pattern analysis algorithms.

Prediction of drug response in breast cancer using integrative experimental/computational modeling.

Nearly 30% of women with early-stage breast cancer develop recurrent disease attributed to resistance to systemic therapy. Prevailing models of chemotherapy failure describe three resistant phenotypes: cells with alterations in transmembrane drug transport, increased detoxification and repair pathways, and alterations leading to failure of apoptosis. Proliferative activity correlates with tumor sensitivity.

Ductal carcinoma in situ: state of the science and roadmap to advance the field.

Purpose: Ductal carcinoma in situ (DCIS) is the fourth leading cancer for women in the United States. Understanding of the biology and clinical behavior of DCIS is imperfect. This article highlights the current knowledge base and the scientific roadmap needed to advance the field.

Clinical, histopathologic, and immunohistochemical features of microglandular adenosis and transition into in situ and invasive carcinoma.

Microglandular adenosis (MGA) of the breast is widely known as a benign lesion that can mimic invasive carcinoma. In situ and invasive carcinomas have been described as arising in MGA, but which cases of MGA will progress to carcinoma is unclear. Criteria for distinguishing uncomplicated MGA, MGA with atypia (AMGA), and carcinoma arising in MGA (MGACA) are not standardized.

A standards based ontological approach to information handling for use by organizations providing human tissue for research.

Tissue resources have become an important component of the infrastructure of institutions as well as companies performing biomedical research. Such tissue resources may be in the model of a bank, collecting a limited type of tissues and processing and storing them following a specific protocol. Such banks or archives may be associated with a clinical study or may function indepedently.

Data mining for gene networks relevant to poor prognosis in lung cancer via backward-chaining rule induction.

We use Backward Chaining Rule Induction (BCRI), a novel data mining method for hypothesizing causative mechanisms, to mine lung cancer gene expression array data for mechanisms that could impact survival. Initially, a supervised learning system is used to generate a prediction model in the form of "IF THEN " style rules. Next, each antecedent (i.