Dysregulation of the epigenome in triple-negative breast cancers: Basal-like and claudin-low breast cancers express aberrant DNA hypermethylation

A subset of human breast cancer cell lines exhibits aberrant DNA hypermethylation that is characterized by hyperactivity of the DNA methyltransferase enzymes, overexpression of DNMT3b, and concurrent methylation-dependent silencing of numerous epigenetic biomarker genes. The objective of this study was to determine if this aberrant DNA hypermethylation (i) is found in primary breast cancers, (ii) is associated with specific breast cancer molecular subtypes, and (iii) influences patient outcomes. Analysis of epigenetic biomarker genes (CDH1, CEACAM6, CST6, ESR1, GNA11, MUC1, MYB, SCNN1A, and TFF3) identified a gene expression signature characterized by reduced expression levels or loss of expression among a cohort of primary breast cancers. The breast cancers that express this gene expression signature are enriched for triple-negative subtypes — basal-like and claudin-low breast cancers. Methylation analysis of primary breast cancers showed extensive promoter hypermethylation of epigenetic biomarker genes among triple-negative breast cancers, compared to other breast cancer subclasses where promoter hypermethylation events were less frequent. Furthermore, triple-negative breast cancers either did not express or expressed significantly reduced levels of protein corresponding to methylation-sensitive biomarker gene products. Together, these findings suggest strongly that loss of epigenetic biomarker gene expression is frequently associated with gene promoter hypermethylation events. We propose that aberrant DNA hypermethylation is a common characteristic of triple-negative breast cancers and may represent a fundamental biological property of basal-like and claudin-low breast cancers. Kaplan–Meier analysis of relapse-free survival revealed a survival disadvantage for patients with breast cancers that exhibit aberrant DNA hypermethylation. Identification of this distinguishing trait among triple-negative breast cancers forms the basis for development of new rational therapies that target the epigenome in patients with basal-like and claudin-low breast cancers.     

Use of Intravenous Thrombolysis in Acute Ischemic Stroke Management in Patients with Active Malignancies: A Topical Review

ObjectivesOur review aims to present existing data on the safety of Intravenous thrombolysis (IVT) use in acute ischemic stroke (AIS) patients with concomitant central nervous system or systemic malignancies, with attention to special circumstances pertaining to specific cancer subtypes to help in acute decision making, especially for neurologists and emergency medicine physicians.MethodsA literature search was conducted on electronic databases inclusive of Medline, EMBASE and CINAHL for articles published or available in English between January 1, 2000 to June 1, 2020 using the following search terms: “acute ischemic stroke,” “cerebrovascular disease,” “Intravenous thrombolysis,” “tissue plasminogen activator,” “cancer patients,” and “neoplasm”.ConclusionRecognition of stroke symptoms in patients with active cancer, in particularly those involving the brain, requires astute clinical judgement. Decision-making can be improved by understanding baseline functional status, cancer prognosis and expected disability from stroke, as well as utilizing diagnostic modalities such acute MRI where needed. While this article does not encourage use of IVT in patients with all malignancies, it lays the groundwork for decision making should thrombolysis be a consideration in a patient with AIS in a cancer patient.     

Delayed presentation of a large congenital laryngeal cleft in an adult

Laryngeal clefts are rare congenital malformations of the posterior laryngotracheal wall that lead to an abnormal communication between the airway and pharyngo-oesophageal tract. The condition is almost universally identified during infancy with minor laryngeal clefts very rarely diagnosed in adulthood. We present our tertiary centre’s experience of a large laryngeal cleft presenting at an advanced age, with the aim of increasing awareness of this correctible cause of respiratory distress and aspiration in adults.     

Multi detector CT Imaging of Abdominal and Diaphragmatic Hernias: Pictorial Essay

Diagnosis of abdominal wall hernia is often a clinical problem, especially in occult or in obese patients. Multidetector CT is an accurate method of detecting various types of abdominal and diaphragmatic hernias. It clearly demonstrates the anatomical sites of hernial sac, its contents and possible complications.     

A comparative evaluation of dermatoglyphics in different classes of malocclusion

Aim

To study associations of dermatoglyphic features with malocclusion in Indian children.

Materials and methods

A total of 237 children aged 12–16 years, who attended our outpatient clinic in a government medical college, were selected. Finger and palm prints were collected, and fingertip pattern frequencies, total ridge counts (TRCs), and atd angles (formed by the triradii below the first and last digits and that in the hypothenar region of the palm) were calculated. These parameters were analyzed with their Angle’s class of malocclusion using appropriate statistical tests. Dermatoglyphic parameters were examined and asymmetry analysis was conducted in subjects with different occlusion patterns.

Results

Although no fingerprint pattern was found to be specific for a particular class of occlusion, increased tendencies toward high frequencies of whorls in subjects with class II malocclusion and plain arches in those with class III malocclusion were observed. Significant differences in atd angle and TRC were observed among malocclusion types (p = 0.0001). Asymmetry scores did not differ significantly.

Conclusion

Dermatoglyphic analysis can be used as an indicator of malocclusion at an early age, thereby aiding the development of treatments aiming to establish favorable occlusion. Inheritance and twin studies, as well as those conducted in different ethnic groups, are required to examine these relationships further.     

Imaging-based algorithmic approach to gallbladder wall thickening

Gallbladder(GB) wall thickening is a frequent finding caused by a spectrum of conditions. It is observed in many extracholecystic as well as intrinsic GB conditions. GB wall thickening can either be diffuse or focal. Diffuse wall thickening is a secondary occurrence in both extrinsic and intrinsic pathologies of GB, whereas, focal wall thickening is mostly associated with intrinsic GB pathologies. In the absence of specific clinical features, accurate etiological diagnosis can be challenging. The survival rate in GB carcinoma(GBC) can be improved if it is diagnosed at an early stage, especially when the tumor is confined to the wall. The pattern of wall thickening in GBC is often confused with benign diseases, especially chronic cholecystitis, xanthogranulomatous cholecystitis, and adenomyomatosis. Early recognition and differentiation of these conditions can improve the prognosis. In this minireview, the authors describe the patterns of abnormalities on various imaging modalities(conventional as well as advanced) for the diagnosis of GB wall thickening. This paper also illustrates an algorithmic approach for the etiological diagnosis of GB wall thickening and suggests a formatted reporting for GB wall abnormalities.