Predictive Biomarkers for Immune Checkpoint Inhibitors in Metastatic Breast Cancer.

We examined a large dataset of female metastatic breast cancers (MBCs) profiled with comprehensive genomic profiling (CGP) to identify the prevalence and distribution of immunotherapy responsiveness-associated biomarkers. DNA was extracted from 3831 consecutive MBCs: 1237 (ER /HER2 ), 1953 ER /HER2 , and 641 triple-negative breast cancer (TNBC). CGP was performed using the FoundationOne or FoundationOne CDx NGS assay.

Identification and Utilization of Biomarkers to Predict Response to Immune Checkpoint Inhibitors.

Immune checkpoint inhibitors (ICPI) have revolutionized cancer therapy and provided clinical benefit to thousands of patients. Despite durable responses in many tumor types, the majority of patients either fail to respond at all or develop resistance to the ICPI. Furthermore, ICPI treatment can be accompanied by serious adverse effects.

Characterization and clinical validation of MCM2 and TOP2A monoclonal antibodies in the BD ProEx™ C assay: An immunoassay which detects aberrant S-phase induction in cervical tissue.

Background: The Papanicolaou (Pap) screen has been successful in reducing cervical cancer; but exhibits low sensitivity when detecting cervical dysplasia. Use of molecular biomarkers in Pap tests may improve diagnostic accuracy.

Design: Monoclonal antibodies to Minichromosome Maintenance Protein 2 (MCM2) and DNA Topoisomerase II α (TOP2A) were selected for use in IHC based on their ability to differentiate normal from diseased cervical tissues in tissue microarrays.

Analytical performance of RNA isolated from BD SurePath™ cervical cytology specimens by the PreTect™ HPV-Proofer assay.

Several commercial HPV ancillary tests are available for detection of E6/E7 RNA. It is not clear how storage of a cervical Pap affects the analytical and clinical performance of the PreTect™ HPV-Proofer assay. To investigate the qualitative performance of RNA extracted from BD SurePath™ liquid-based cytology (LBC) specimens for the detection of human papillomavirus (HPV) E6/E7 mRNA using the PreTect™ HPV-Proofer assay, studies including stability, reproducibility, residual specimen analysis, and storage medium comparison assays were performed.

Role of protein biomarkers in the detection of high-grade disease in cervical cancer screening programs.

Since the Pap test was introduced in the 1940s, there has been an approximately 70% reduction in the incidence of squamous cell cervical cancers in many developed countries by the application of organized and opportunistic screening programs. The efficacy of the Pap test, however, is hampered by high interobserver variability and high false-negative and false-positive rates. The use of biomarkers has demonstrated the ability to overcome these issues, leading to improved positive predictive value of cervical screening results.

Novel and recurrent EMD mutations in patients with Emery-Dreifuss muscular dystrophy, identify exon 2 as a mutation hot spot.

Emery-Dreifuss muscular dystrophy (EDMD) is a neuromuscular disorder exhibiting a cardiomyopathy with cardiac conduction defects. X-linked EDMD arises from mutations in the EMD gene, which encodes for a nuclear membrane protein termed emerin. In this study, we describe novel and recurrent EMD mutations identified in 18 probands and three carriers from a cohort of 255 North American patients referred for EDMD genetic mutation analysis.

Novel LMNA mutations in patients with Emery-Dreifuss muscular dystrophy and functional characterization of four LMNA mutations.

Mutations in LMNA cause a variety of diseases affecting striated muscle including autosomal Emery-Dreifuss muscular dystrophy (EDMD), LMNA-associated congenital muscular dystrophy (L-CMD), and limb-girdle muscular dystrophy type 1B (LGMD1B). Here, we describe novel and recurrent LMNA mutations identified in 50 patients from the United States and Canada, which is the first report of the distribution of LMNA mutations from a large cohort outside Europe. This augments the number of LMNA mutations known to cause EDMD by 16.

Recovery of DNA from BD SurePath cytology specimens and compatibility with the Roche AMPLICOR Human Papillomavirus (HPV) Test.

Background: The AMPLICOR HPV Test has been validated for use with cervical cells collected in liquid-based preservative fluids, such as BD SurePath. It is currently recommended, however, that residual BD SurePath samples be stored at 4 degrees C prior to testing.

Objectives: The aim of this study was to demonstrate that DNA isolated from SurePath cervical cytology specimens and stored at ambient temperature was also compatible with the AMPLICOR HPV Test.

Isolation of RNA from cell lines and cervical cytology specimens stored in BD SurePath preservative fluid and downstream detection of housekeeping gene and HPV E6 expression using real time RT-PCR.

This study was performed to demonstrate that RNA isolated from cell lines and cervical cytology specimens stored in SurePath preservative fluid would be functional in real-time RT-PCR assays. RNA was isolated from cervical cell lines or cytology samples stored in SurePath preservative at room temperature for 2-5 weeks using five commercially available RNA purification kits, three of which contain proteinases. The quality of the RNA was assessed by real time RT-PCR amplification of GAPDH, GUSB, U1A, HPV 16 and 18 E6 mRNAs.

Isolation of RNA from residual BD SurePath liquid-based cytology specimens and detection of HPV E6/E7 mRNA using the PreTectt HPV-Proofer assay.

Infection with high-risk human papillomavirus (HPV) is known to be associated directly with the development of cervical cancer. Recent data suggests that the detection of E6/E7 mRNA from high-risk HPV types may serve as a better diagnostic method for detecting the presence of cervical pre-cancer than HPV DNA testing. This report details a commercially available nucleic acid isolation protocol which can be used to isolate reproducibly RNA from residual BD SurePath liquid-based cytology specimens stored for up to 28 days, and have demonstrated the quality and quantity of mRNA is sufficient for detection with the NorChip PreTect HPV-Proofer assay.

Limb-girdle muscular dystrophy in the United States.

Limb-girdle muscular dystrophy (LGMD) has been linked to 15 chromosomal loci, 7 autosomal-dominant (LGMD1A to E) and 10 autosomal-recessive (LGMD2A to J). To determine the distribution of subtypes among patients in the United States, 6 medical centers evaluated patients with a referral diagnosis of LGMD. Muscle biopsies provided histopathology and immunodiagnostic testing, and their protein abnormalities along with clinical parameters directed mutation screening.

Lamins A and C are differentially dysfunctional in autosomal dominant Emery-Dreifuss muscular dystrophy.

Mutations in the LMNA gene, which encodes nuclear lamins A and C by alternative splicing, can give rise to Emery-Dreifuss muscular dystrophy. The mechanism by which lamins A and C separately contribute to this molecular phenotype is unknown. To address this question we examined ten LMNA mutations exogenously expressed as lamins A and C in COS-7 cells.

The diagnosis of Trichomonas vaginalis in liquid-based Pap tests: correlation with PCR.

The conventional Papanicolaou smear (CPS) is not considered accurate for the diagnosis of Trichomonas vaginalis (T. vaginalis), and women noted to carry the organism on CPS are recommended to undergo confirmatory testing. Liquid-based preparations have been shown to facilitate the diagnosis of squamous lesions and may also facilitate the diagnosis of T.

Low prevalence of loss of heterozygosity and SMAD4 mutations in sporadic and familial juvenile polyposis syndrome-associated juvenile polyps.

Background: Juvenile polyps (JP) may develop sporadically or may be associated with the familial juvenile polyposis syndrome (FJPS). In FJPS, the epithelium is susceptible to dysplasia and, ultimately adenocarcinoma. However, the mechanisms involved in this transformation are unknown.

Graft-vs-host disease after solid organ transplant.

We identified 10 solid organ transplant recipients with a histologic diagnosis of graft-vs-host disease (GVHD). Histologic slides were reviewed, and information on the transplant, HLA match, and blood product transfusion history was obtained. Molecular testing to evaluate the presence of donor lymphocytes (chimerism) was done in 1 case.

Molecular alterations in chronic ulcerative colitis-associated and sporadic hyperplastic polyps: a comparative analysis.

Objectives: There is growing interest in the biological and molecular features and neoplastic potential of colonic hyperplastic polyps because of the recent finding of K-ras mutations in many of these lesions. Hyperplastic polyps may also develop in chronic ulcerative colitis (CUC), but it is unclear if these are biologically similar to the sporadic type. The aim of this study was to evaluate and compare the molecular profile of CUC-associated hyperplastic polyps with sporadic hyperplastic polyps of the colon.

Genetic alterations in serrated adenomas: comparison to conventional adenomas and hyperplastic polyps.

Serrated adenoma is a recently described entity characterized by the presence of a hyperplastic (serrated) growth pattern combined with cytologic features of dysplasia. In contrast to conventional (nonserrated) adenomas, the molecular features of serrated adenomas have been poorly studied. Thus, it remains unclear if serrated adenomas are simply a morphologic variant of conventional adenomas or represent a different biologic entity.

Genetic alterations of Carney complex are not present in sporadic cardiac myxomas.

Cardiac myxomas are the most frequent cardiac tumors and cause for significant morbidity and mortality. Recent evidence indicates that cardiac myxomas are, in fact, neoplasms rather than organized thrombi. Cardiac myxomas may present as solitary lesions or in association with the Carney complex.