Congenital acinar dysplasia: a lethal entity

Congenital acinar dysplasia is a lethal, developmental lung malformation resulting in neonatal respiratory insufficiency. This entity is characterized by pulmonary hypoplasia and arrest in the pseudoglandular stage of development, resulting in the absence of functional gas exchange. The etiology is unknown, but a relationship with the disruption of the TBX4-FGF10 pathway has been described. There are no definitive antenatal diagnostic tests. It is a diagnosis of exclusion from other diffuse embryologic lung abnormalities with identical clinical presentations that are, however, histopathologically distinct

Reduced Androgen Receptor Expression Accelerates the Onset of ERBB2 Induced Breast Tumors in Female Mice

Androgen receptor (AR) is commonly expressed in both the epithelium of normal mammary glands and in breast cancers. AR expression in breast cancers is independent of estrogen receptor alpha (ERα) status and is frequently associated with overexpression of the ERBB2 oncogene. AR signaling effects on breast cancer progression may depend on ERα and ERBB2 status. Up to 30% of human breast cancers are driven by overactive ERBB2 signaling and it is not clear whether AR expression affects any steps of tumor progression in this cohort of patients. To test this, we generated mammary specific Ar depleted mice (MARKO) by combining the floxed allele of Ar with the MMTV-cre transgene on an MMTV-NeuNT background and compared them to littermate MMTV-NeuNT, Arfl/+ control females. Heterozygous MARKO females displayed reduced levels of AR in mammary glands with mosaic AR expression in ductal epithelium. The loss of AR dramatically accelerated the onset of MMTV-NeuNT tumors in female MARKO mice. In this report we show that accelerated MMTV-NeuNT-dependent tumorigenesis is due specifically to the loss of AR, as hormonal levels, estrogen and progesterone receptors expression, and MMTV-NeuNT expression were similar between MARKO and control groups. MMTV-NeuNT induced tumors in both cohorts displayed distinct loss of AR in addition to ERα, PR, and the pioneer factor FOXA1. Erbb3 mRNA levels were significantly elevated in tumors in comparison to normal mammary glands. Thus the loss of AR in mouse mammary epithelium accelerates malignant transformation rather than the rate of tumorigenesis

Solitary neurofibroma of the breast

Neurofibromas are slow-growing, painless, benign nerve-sheath tumors. They occur most commonly in the dermis and subcutis and are rarely found in the breast. We report a rare case of a solitary neurofibroma of the breast in a 61-year-old asymptomatic woman

Comparison of Performance Characteristics of Oval Cup Forceps Versus Serrated Jaw Forceps in Gastric Biopsy

Obtaining quality endoscopic biopsy specimens is vital in making successful histological diagnoses. The influence of forceps cup shape and size on quality of biopsy specimens is unclear. To identify whether oval cup or two different serrated jaw biopsy forceps could obtain specimens of superior size. Secondary endpoints were tissue adequacy, depth of tissue acquisition, and crush artifact. A single-center, prospective, pathologist-masked, randomized controlled trial was performed. In total 136 patients with a clinical indication for esophagogastroduodenoscopy with biopsy were randomized to receive serial biopsies with a large-capacity serrated forceps with jaw diameter 2.2 mm (SER1) and either a large-capacity oval forceps with jaw diameter 2.4 mm (OVL) or large-capacity serrated biopsy forceps with jaw diameter 2.4 mm (SER2) in two parallel groups. SER2 provided significantly larger specimens than did the other forceps (SER2 3.26 ± 1.09 vs. SER1 2.92 ± 0.88 vs. OVL 2.92 ± 0.76; p = 0.026), with an average size difference of 0.34 mm greater with SER2 compared to SER1 and OVL. OVL provided significantly deeper biopsies compared to SER1 and SER2 (p = 0.02), with 31 % of OVL biopsies reaching the submucosa. SER2 had significantly less crush artifact than SER1 and OVL (p < 0.0001). Serrated forceps provided larger samples compared to oval jaw forceps of the same size, with SER2 providing the largest specimen size. Oval cup forceps had deeper penetration of epithelium, while the larger jaw diameter serrated jaw forceps had less crush artifact. All three forceps provided specimens adequate for diagnostic purposes

Downstream targets of steroid receptors are reduced in MMTV-NeuNT tumors.

<p>Tumors and non-tumor bearing mammary glands were evaluated for the expression of ERα and PR downstream target genes. Expression of each gene was normalized to 18S. Gene expression in tumors for MARKO and Control mice and normal MARKO glands were normalized to expression in non-tumor bearing control mammary glands (Control normal = 26, Control Tumor = 9, MARKO normal = 15 and MARKO tumor = 7). Reduced expression was seen in tumors compared to normal tissue for <i>Areg</i> (A), <i>Rankl</i> (B), <i>Wnt4</i> (C) and <i>Foxa1</i> (D). ***P<0.005, for normal versus tumor expression.</p

Control and MARKO mice show similar proliferation in the normal mammary gland.

<p>Representative pictures of normal Control (A) (n = 4) and MARKO (B) (n = 4) mammary glands stained for Ki67. Arrowheads denote Ki67 positive cells. C. Ki67 staining was quantified and is shown as the percentage of total epithelial cells positive and negative for Ki67 staining. Scale bar = 20 µm.</p

Characterization of mice with conditional knockout of AR in mammary glands (MARKO).

<p>A. Breeding strategy used to create experimental cohorts. Two generation breeding was used to produce tumor-prone MMTV-NeuNT (activated rat ERBB2) transgenic MARKO (male and females underlined on the left side) and Control (underlined on the right) mice. MARKO mice are positive for MMTV-cre transgene, specifically expressed in mammary glands. B. Recombination events in the genomic DNA from mammary ductal tissue dissociated from fat cells. Top band (952 bp) is derived from the non-recombined floxed <i>Ar^fl</i> allele, middle band (855 bp) is from the wild-type <i>Ar⁺</i> allele, and the lower band (404 bp) is an amplicon derived from the <i>Ar^Δ</i> allele, resulting from Cre/LoxP induced deletion of exon 2. <i>Ar^fl/+</i> is a positive control for the floxed allele and WT is wild-type (<i>Ar⁺/Ar⁺</i>). Left panel is recombination in male mice and the right panel is recombination in female mice. No recombination is observed in mice lacking MMTV-cre (lanes 1 and 4), the deleted allele is present in mice with MMTV-cre (lanes 2 and 3) C. Reduced number of AR positive luminal epithelial cells in MARKO mammary glands. AR positive luminal epithelial cells in the mammary glands of Control (n = 5) and MARKO (n = 5) mice were counted and determined as a percentage of the total number of cells per gland (p = 0.0019). An average of 260 cells were counted per individual mouse. Immunohistochemical staining for AR expression in Control (D) and MARKO (E and F) mammary glands. Scale bar = 20 µm.</p