QRICH1 variants in Ververi‐Brady syndrome—delineation of the genotypic and phenotypic spectrum

Ververi‐Brady syndrome (VBS, # 617982) is a rare developmental disorder, and loss‐of‐function variants in QRICH1 were implicated in its etiology. Furthermore, a recognizable phenotype was proposed comprising delayed speech, learning difficulties and dysmorphic signs. Here, we present four unrelated individuals with one known nonsense variant (c.1954C > T; p.[Arg652*]) and three novel de novo QRICH1 variants, respectively. These included two frameshift mutations (c.832_833del; p.(Ser278Leufs*25), c.1812_1813delTG; p.(Glu605Glyfs*25)) and interestingly one missense mutation (c.2207G > A; p.[Ser736Asn]), expanding the mutational spectrum. Enlargement of the cohort by these four individuals contributes to the delineation of the VBS phenotype and suggests expressive speech delay, moderate motor delay, learning difficulties/mild ID, mild microcephaly, short stature and notable social behavior deficits as clinical hallmarks. In addition, one patient presented with nephroblastoma. The possible involvement of QRICH1 in pediatric cancer assumes careful surveillance a key priority for outcome of these patients. Further research and enlargement of cohorts are warranted to learn about the genetic architecture and the phenotypic spectrum in more detail.     

alphaB-crystallin is a marker of aggressive breast cancer behavior but does not independently predict for patient outcome: a combined analysis of two randomized studies

Background

alphaB-crystallin is a small heat shock protein that has recently been characterized as an oncoprotein correlating with the basal core phenotype and with negative prognostic factors in breast carcinomas. The purpose of this study was to evaluate alphaB-crystallin with respect to clinicopathological parameters and the outcome of patients with operable high-risk breast cancer.

Methods

A total of 940 tumors were examined, derived from an equal number of patients who had participated in two randomized clinical trials (paclitaxel-containing regimen in 793 cases). Immunohistochemistry for ER, PgR, HER2, Ki67, CK5, CK14, CK17, EGFR, alphaB-crystallin, BRCA1 and p53 was performed. BRCA1 mutation data were available in 89 cases.

Results

alphaβ-crystallin was expressed in 170 cases (18.1%) and more frequently in triple-negative breast carcinomas (TNBC) (45% vs. 14.5% non-TNBC, p <?0.001). alphaB-crystallin protein expression was significantly associated with high Ki67 (Pearson chi-square test, p <?0.001), p53 (p =?0.002) and basal cytokeratin protein expression (p <?0.001), BRCA1 mutations (p =?0.045) and negative ER (p <?0.001) and PgR (p <?0.001). Its overexpression, defined as >30% positive neoplastic cells, was associated with adverse overall survival (Wald’s p =?0.046). However, alphaB-crystallin was not an independent prognostic factor upon multivariate analysis. No interaction between taxane-based therapy and aβ-crystallin expression was observed.

Conclusions

In operable high-risk breast cancer, alphaB-crystallin protein expression is associated with poor prognostic features indicating aggressive tumor behavior, but it does not seem to have an independent impact on patient survival or to interfere with taxane-based therapy.

Trial registrations

ACTRN12611000506998 (HE10/97 trial) andACTRN12609001036202 (HE10/00 trial).

     

Masses of myeloadipose tissue: radiological and clinical considerations

The records of 30 patients presenting radiological evidence of masses of extramedullary myeloadipose (hemopoietic) tissue, 25 patients suffering from thalassemia, one from sickle-cell anemia, and one from myelofibrosis were studied. Three patients presented with primary myelolipomas. Most of the patients with thalassemia presented with masses of hemopoiesis in the costovertebral angle and five patients presented with spinal cord compression. Magnetic resonance imaging is the best method for visualization and assessment of the extent of the masses in the thorax and spinal canal. Radiotherapy is the treatment of choice for spinal cord compression. One patient with thalassemia and one patient with myelofibrosis presented with masses of extramedullary hemopoiesis in the adrenals. All five patients with masses of myeloadipose tissue in the adrenals were treated surgically.     

Dexamethasone decreases the transmesothelial electrical resistance of the parietal and visceral pleura

The effect of dexamethasone on the transmesothelial electrical resistance (R _TM) of sheep pleura was investigated by Ussing chamber experiments. Our results show that dexamethasone decreases the R _TM of sheep pleurae, in part by stimulation of glucocorticoid receptors. This finding may be of importance in regard to the faster resolution of corticosteroid-treated pleural effusions.     

Angiomatoid fibrous histiocytoma with cystic structures of sweat duct origin

Angiomatoid fibrous histiocytoma is an unusual soft tissue tumor, mostly arising in the subcutaneous fibro-adipose tissue of children and young adults and measuring a few centimeters in greatest dimension. Reported herein is a unique case of angiomatoid fibrous histiocytoma containing epithelium-lined cystic structures. This large tumor (12 cm) was located in the subcutaneous tissue of the left leg of a 28-year-old woman. The cystic structures were variably sized and were lined by a double cell layer with areas of squamous metaplasia. Their overall histological features suggested a sweat duct origin. Immunohistochemical stains confirmed such origin, demonstrating an inner epithelial and an outer myoepithelial (smooth muscle actin and cytokeratin 17 positive) cell layer. The present case is illustrative of a mechanism of sweat duct dilatation that may occur during the growth of neoplasms involving the dermis and subcutis, resulting in formation of tumors with unusual histological features.     

Cytotoxicity of a New Calcium Silicate Endodontic Sealer

Introduction

Resin sealers with biocompatible and bioactive additives have been used in clinical practice. Recently, a calcium silicate root canal sealer was introduced under the name BioRoot RCS (Septodont, Saint Maur-des-Fossés, France). The aim of this study was to evaluate the effects of BioRoot RCS on cell survival and proliferation of cultured cells in parallel with an epoxy resin sealer with calcium phosphate and calcium oxide and a salicylate resin sealer with mineral trioxide aggregate filler. The tested hypothesis was that BioRoot RCS is significantly less cytotoxic than the other tested sealers.