Activity of trastuzumab emtansine (T-DM1) in 3D cell culture.

Background: Cell spheroids and aggregates generated from three-dimensional (3D) cell culture methods are similar to in vivo tumors in terms of tissue morphology, biology, and gene expression, unlike cells grown in 2D cell cultures. Breast cancer heterogeneity is one of the main drug resistant mechanisms and needs to be overcome in order to increase the efficacy of drug activity in its treatments.

Methods: We performed a unique 3D cell culture and drug efficacy study with trastuzumab emtansine (Kadcyla®, T-DM1) across five breast cancer cell lines (BT-474, SK-BR-3, MDA-MB-361, MDA-MB-175, and MCF-7) that were previously investigated in 2D cell culture.

Intratumoral Estrogen Receptor Heterogeneity of Expression in Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer as Evaluated by a Brightfield Multiplex Assay.

Breast cancer (BC) is a heterogeneous disease with evolving genetic alterations and expressions of receptor proteins. Intratumoral heterogeneity (ITH) is considered to be a resistance factor in response to targeted therapies. The current single-slide, single-marker immunohistochemistry techniques cannot accurately assess ITH at the individual cancer cell level.

Development of a PD-L1 Complementary Diagnostic Immunohistochemistry Assay (SP142) for Atezolizumab.

Cancer immunotherapies, such as atezolizumab, are proving to be a valuable therapeutic strategy across indications, including non-small cell lung cancer (NSCLC) and urothelial cancer (UC). Here, we describe a diagnostic assay that measures programmed-death ligand 1 (PD-L1) expression, via immunohistochemistry, to identify patients who will derive the most benefit from treatment with atezolizumab, a humanized monoclonal anti-PD-L1 antibody. We describe the performance of the VENTANA PD-L1 (SP142) Assay in terms of specificity, sensitivity, and the ability to stain both tumor cells (TC) and tumor-infiltrating immune cells (IC), in NSCLC and UC tissues.

A Proposed Set of Metrics to Reduce Patient Safety Risk From Within the Anatomic Pathology Laboratory.

Background: Anatomic pathology laboratory workflow consists of 3 major specimen handling processes. Among the workflow are preanalytic, analytic, and postanalytic phases that contain multistep subprocesses with great impact on patient care. A worldwide representation of experts came together to create a system of metrics, as a basis for laboratories worldwide, to help them evaluate and improve specimen handling to reduce patient safety risk.

Validation of an electronic program for pathologist training in the interpretation of a complex companion diagnostic immunohistochemical assay.

Companion diagnostics assay interpretation can select patients with the greatest targeted therapy benefits. We present the results from a prospective study demonstrating that pathologists can effectively learn immunohistochemical assay-interpretation skills from digital image-based electronic training (e-training). In this study, e-training was used to train board-certified pathologists to evaluate non-small cell lung carcinoma for eligibility for treatment with onartuzumab, a MET-inhibiting agent.

HER2 intratumoral heterogeneity analyses by concurrent HER2 gene and protein assessment for the prognosis of HER2 negative invasive breast cancer patients.

HER2 gene-protein assay (GPA) is a new method for the simultaneous evaluation of HER2 immunohistochemistry (IHC) and HER2 dual in situ hybridization (DISH) on single tissue sections of breast cancer. We investigated the presence of HER2 gene and protein discrepancy and HER2-heterogeneity using HER2-GPA. HER2 status was analyzed for the correlation between the presence of HER2-heterogeneity and patient prognosis.

The assessment of HER2 status in breast cancer: the past, the present, and the future.

Humanized monoclonal anti-human growth factor receptor 2 (HER2) antibody trastuzumab was approved for HER2 positive breast cancer patient treatment 11 years after the demonstration of HER2 gene amplification associated with the HER2 protein overexpression in breast cancer in 1987. HER2 positive status of breast cancer patients is assessed by HER2 gene amplification with in situ hybridization (ISH) and/or HER2 protein overexpression with immunohistochemistry (IHC). Because the discordance between quantitative HER2 ISH and subjective, semi-quantitative HER2 IHC assay results is a well-recognized issue of HER2 testing, we developed an assay combining HER2 ISH and HER2 IHC assays (HER2 gene-protein assay; HER2 GPA) as one test on the same tissue section.

Therapeutic Area Data Standards for Autosomal Dominant Polycystic Kidney Disease: A Report From the Polycystic Kidney Disease Outcomes Consortium (PKDOC).

Data standards provide a structure for consistent understanding and exchange of data and enable the integration of data across studies for integrated analysis. There is no data standard applicable to kidney disease. We describe the process for development of the first-ever Clinical Data Interchange Standards Consortium (CDISC) data standard for autosomal dominant polycystic kidney disease (ADPKD) by the Polycystic Kidney Disease Outcomes Consortium (PKDOC).

A novel gene-protein assay for evaluating HER2 status in gastric cancer: simultaneous analyses of HER2 protein overexpression and gene amplification reveal intratumoral heterogeneity.

Background: Human epidermal growth factor receptor 2 (HER2) protein overexpression and gene amplification are important biomarkers for trastuzumab treatment in breast and gastric cancer patients. Gastric cancer presents high rates of tumor heterogeneity, which may influence the results of HER2 testing. A novel gene-protein assay (GPA) can allow the simultaneous analysis of HER2 protein and gene status on a single slide.

Overlapping upper and lower gastrointestinal symptoms in irritable bowel syndrome patients with constipation or diarrhea.

Objectives: Distinguishing between irritable bowel syndrome (IBS) and functional dyspepsia can be challenging because of the variations in symptom patterns, which commonly overlap. However, the overlap is poorly quantified, and it is equally uncertain whether symptom patterns differ in subgroups of IBS arbitrarily defined by primary bowel patterns of constipation (IBS-C) and diarrhea (IBS-D). We aimed to determine and to compare the distribution of GI symptoms, both, upper and lower, among IBS-C and IBS-D patients.