Gene expression profiling of primary male breast cancers reveals two unique subgroups and identifies N-acetyltransferase-1 (NAT1) as a novel prognostic biomarker.

Introduction: Male breast cancer (MBC) is a rare and inadequately characterized disease. The aim of the present study was to characterize MBC tumors transcriptionally, to classify them into comprehensive subgroups, and to compare them with female breast cancer (FBC).

Methods: A total of 66 clinicopathologically well-annotated fresh frozen MBC tumors were analyzed using Illumina Human HT-12 bead arrays, and a tissue microarray with 220 MBC tumors was constructed for validation using immunohistochemistry.

Identification of new microRNAs in paired normal and tumor breast tissue suggests a dual role for the ERBB2/Her2 gene.

To comprehensively characterize microRNA (miRNA) expression in breast cancer, we performed the first extensive next-generation sequencing expression analysis of this disease. We sequenced small RNA from tumors with paired samples of normal and tumor-adjacent breast tissue. Our results indicate that tumor identity is achieved mainly by variation in the expression levels of a common set of miRNAs rather than by tissue-specific expression.

High-resolution genomic profiling of male breast cancer reveals differences hidden behind the similarities with female breast cancer.

Male breast cancer (MBC) is extremely rare and poorly characterized on the molecular level. Using high-resolution genomic data, we aimed to characterize MBC by genomic imbalances and to compare it with female breast cancer (FBC), and further to investigate whether the genomic profiles hold any prognostic information. Fifty-six fresh frozen MBC tumors were analyzed using high-resolution tiling BAC arrays.

Genomic subtypes of breast cancer identified by array-comparative genomic hybridization display distinct molecular and clinical characteristics.

Introduction: Breast cancer is a profoundly heterogeneous disease with respect to biologic and clinical behavior. Gene-expression profiling has been used to dissect this complexity and to stratify tumors into intrinsic gene-expression subtypes, associated with distinct biology, patient outcome, and genomic alterations. Additionally, breast tumors occurring in individuals with germline BRCA1 or BRCA2 mutations typically fall into distinct subtypes.

Identification of subtypes in human epidermal growth factor receptor 2--positive breast cancer reveals a gene signature prognostic of outcome.

PURPOSE Human epidermal growth factor receptor 2 (HER2) gene amplification or protein overexpression (HER2 positivity) defines a clinically challenging subgroup of patients with breast cancer (BC) with variable prognosis and response to therapy. We aimed to investigate the heterogeneous biologic appearance and clinical behavior of HER2-positive tumors using molecular profiling. PATIENTS AND METHODS Hierarchical clustering of gene expression data from 58 HER2-amplified tumors of various stage, histologic grade, and estrogen receptor (ER) status was used to construct a HER2-derived prognostic predictor that was further evaluated in several large independent BC data sets.

Numb protein expression correlates with a basal-like phenotype and cancer stem cell markers in primary breast cancer.

Decreased expression of Numb, resulting in activation of the proto-oncogene Notch1 and reduction in the tumor suppressor p53, has been demonstrated in mammary carcinomas. The aim of this study was to investigate the relationship between Numb protein expression and clinicopathological characteristics, tumor biological subtypes and putative cancer stem cell markers in a well-characterized cohort of primary human breast cancers. Immunohistochemistry was performed on tissue microarrays of primary invasive breast tumors using a polyclonal anti-Numb primary antibody.

Islet beta-cell area and hormone expression are unaltered in Huntington's disease.

Neurodegenerative disorders are often associated with metabolic alterations. This has received little attention, but might be clinically important because it can contribute to symptoms and influence the course of the disease. Patients with Huntington's disease (HD) exhibit increased incidence of diabetes mellitus (DM).

Distinct genomic profiles in hereditary breast tumors identified by array-based comparative genomic hybridization.

Mutations in BRCA1 and BRCA2 account for a significant proportion of hereditary breast cancers. Earlier studies have shown that inherited and sporadic tumors progress along different somatic genetic pathways and that global gene expression profiles distinguish between these groups. To determine whether genomic profiles similarly discriminate among BRCA1, BRCA2, and sporadic tumors, we established DNA copy number profiles using comparative genomic hybridization to BAC-clone microarrays providing <1 Mb resolution.

Nitric Oxide Synthase in Human Parathyroid Glands and Parathyroid Adenomas.

Nitric oxide (NO) is a novel gaseous intercellular transmitter thought to play important physiological roles in the regulation of blood flow and hormone secretion in, for example, the pituitary, the thyroid, and the endocrine pancreas. Whether nitric oxide synthase (NOS) is present in the human parathyroid glands has not yet been demonstrated. In the present study, histologically normal, but functionally suppressed human parathyroid glands and parathyroid adenomas from patients with primary hyperparathyroidism were investigated by immunocytochemistry with antibodies against neuronal NOS and by reduced nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase histochemistry.