Skin barrier in atopic dermatitis: beyond filaggrin

Abstract: Atopic dermatitis is a chronic inflammatory skin disease with a complex pathogenesis, where changes in skin barrier and imbalance of the immune system are relevant factors. The skin forms a mechanic and immune barrier, regulating water loss from the internal to the external environment, and protecting the individual from external aggressions, such as microorganisms, ultraviolet radiation and physical trauma. Main components of the skin barrier are located in the outer layers of the epidermis (such as filaggrin), the proteins that form the tight junction (TJ) and components of the innate immune system. Recent data involving skin barrier reveal new information regarding its structure and its role in the mechanic-immunological defense; atopic dermatitis (AD) is an example of a disease related to dysfunctions associated with this complex.

Pattern of human epidermal growth factor receptor 2 [HER2] expression in invasive breast carcinoma, immunohistochemical - study on patients in Upper Egypt

Breast cancer is a major public health problem throughout the world. It accounts for 38% of all new cancer cases among women living in Egypt. One of the most important prognostic and determinant factor of the line of its treatment is the human epidermal growth factor receptor 2 [HER2], it is associated with the more aggressive phenotype. Attention has been focused on the expression of HER2 receptor proteins in breast cancer cells especially its membranous domain, it resulted in variable results concerning its percentage of expression as well as its geographic distribution. So there is a need to study HER2 types of expression in breast cancer patients in our location as well as its correlation with the clinicopathological parameters. HER2 expression in 336 retrospective breast cancer specimens was examined immunohistochemically using tissue microarray. Expression was scored into 0, 1, 2 and 3 degrees and was correlated with clinicopathological criteria. HER2 expression in our specimens showed both membranous and cytoplasmic staining patterns. 18.6% of specimens showed membranous immunoreactivity and 74.1% specimens showed cytoplasmic staining pattern. Significant statistical association was found between cytoplasmic staining of HER2 and tumors of low grade, ER positivity [p<0.001, 0.001, 0.008] respectively. There was statistical significance difference between high membranous expression of HER2 and ER negativity [p=0.038], but our results didn't find significant difference with tumor size, lymphvascular invasion or lymph node metastasis. The frequency of high membranous expression of HER2 in our specimens is 18.6% and inversely correlated with ER positive tumors. This group of patients should be subjected to specific treatment with Trastuzumab, to improve their survival. Surprisingly cutoplasmic expression detected in most of our patients with frequency of 74.1% with positive relationship to low tumor grade and hormone receptor positive tumors. Since this group of patients may be resistant to trastuzumab and need specific treatment with tyrosine kinase drug inhibitors, this observation is going to be discussed and need to be followed up in the future