Normal human breast tissue consists of epithelial and nonepithelial cells with different molecular profiles and differentiation grades. This molecular heterogeneity is known to yield abnormal clones that may contribute to the development of breast carcinomas. Stem cells that are found in developing and mature breast tissue are either positive or negative for cytokeratin 19 depending on their subtype. These cells are able to generate carcinogenesis along with mature cells. However, scientific data remains controversial regarding the monoclonal or polyclonal origin of breast carcinomas. The majority of breast carcinomas originate from epithelial cells that normally express BRCA1. The consecutive loss of the BRCA1 gene leads to various abnormalities in epithelial cells. Normal breast epithelial cells also express hypoxia inducible factor (HIF) 1α and HIF-2α that are associated with a high metastatic rate and a poor prognosis for malignant lesions. The nuclear expression of estrogen receptor (ER) and progesterone receptor (PR) in normal human breast tissue is maintained in malignant tissue as well. Several controversies regarding the ability of ER and PR status to predict breast cancer outcome remain. Both ER and PR act as modulators of cell activity in normal human breast tissue. Ki-67 positivity is strongly correlated with tumor grade although its specific role in applied therapy requires further studies. Human epidermal growth factor receptor 2 (HER2) oncoprotein is less expressed in normal human breast specimens but is highly expressed in certain malignant lesions of the breast. Unlike HER2, epidermal growth factor receptor expression is similar in both normal and malignant tissues. Molecular heterogeneity is not only found in breast carcinomas but also in normal breast tissue. Therefore, the molecular mapping of normal human breast tissue might represent a key research area to fully elucidate the mechanisms of breast carcinogenesis.

Crosstalk between angiogenesis and lymphangiogenesis in embryonic development continues during postnatal life and has specific mechanisms involving factors that initiate activation of the intracellular cascade for their specific receptors. Platelet-derived growth factors (PDGFs) and their corresponding receptors (PDGFRs) are known as important regulators of blood vessel development in both normal and pathologic angiogenesis. Despite some recent papers which reported a potential role of the PDGF/PDGFR axis in lymphatic spread of tumor cells, a few papers have suggested the potential role of PDGFs in tumor lymphangiogenesis development. The present paper summarizes the potential lymphangiogenic role of the PDGF/PDGFR axis, underlying upcoming challenges in the field.

Introduction: S100 protein and GFAP expression in pituitary adenomas tumour cells is not well known; few correlations with other prognostic or therapeutic factors have previously been reported in pituitary adenomas. We aim to elucidate their involvement in the pathogenesis of pituitary adenomas and to establish the correlation of their expression with different growth factors and growth factor receptors known to have a prognostic and/or therapeutic role. Material and methods: Sixty-one cases of pituitary adenomas were immunohistochemically assessed for the expression of GFAP and S100 protein in both tumour cells and FS cells, in close relationship with hormone profile, and correlated with vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) expression, previously studied by our team. Results: GFAP and S100 protein were expressed both in tumour cells and FS cells. Differences between morphology, distribution, and density of GFAP+ FS cells and S100+ FS cells were observed according to the hormone profile of pituitary adenomas. GFAP and S100 protein expression in tumour cells was significantly related to hormone profile of pituitary adenomas and also with VEGF and EGFR expression. Conclusions: GFAP and S100 protein expressions in tumour cells from pituitary adenomas are influenced by hormone profile. Our results support the presence of two molecular subtypes of FS cells GFAP+/VEGF+/S100 respectively and another one that is GFAP-/S100+/ /EGFR+ simultaneously with the classical variant GFAP+/S100+. It is possible that S100+/EGFR+ pituitary adenomas represent a group of pituitary adenomas with an aggressive behaviour and a high ability of invasion and recurrence. (Endokrynol Pol 2017; 68 (4): 380-389)

Abstract. Aim Peripheral nerve injuries are a challenge for both the surgeon and the clinician, a challenge supported by the absence of evaluation markers for post-traumatic healing. This challenge is maintained due to the structural particularities and the difficulties of peripheral nerve biopsy sampling following surgical intervention. Currently, no serum marker that could be used as an evaluation biomarker for nerve regeneration is available; moreover; the correlation between motor rehabilitation and the morphological sequences that form the basis of this recovery have been very little studied and are poorly understood, most of them being rarely reported in experimental models of nerve regeneration.Protein S100 is specific and able to identify mature Schwann cells; neurofilament associated protein (NFAP) is applied for the identification of intra-axonal intermediate filaments. In the study of nerve regeneration, glial fibrillary acidic protein (GFAP) seems to mark reactive Schwann cells and is normally expressed only in the glial cells of the central nervous system. Very few clinical data and case reports are available regarding nerve regeneration tested through usage of GFAP. In pathology, GFAP is expressed in peripheral nerve sheath tumors (malignant schwannomas) (1). Recent studies that used rat experimental models have shown that differentiated Schwann-like stem cells from adipose tissue (AdSC) were positive for GFAP expression. Study of their morphological features have demonstrated that these AdSC-derived GFAP-positive cells exhibited a bipolar, tripolar and even multipolar structure, presented a single layer growth pattern, but were characterized by a flattened morphology, large dimensions and thin expansions (2). The majority of these cells proved to be highly proliferative in the aforementioned study, the percentage of such differentiated cells from the adipose tissue was over 95% (3). This study did not establish a correlation between the percentage of Schwann-like GFAP-positive cells and muscle volume restoration. Regarding this aspect, we considered the utility of the evaluation of the presence as well as the distribution of corresponding GFAP-positive cells in the muscle, taking into account that such an evaluation has not yet been reported in the scientific literature.NFAP marks intermediate filaments located in the inner part of a severed axon, thus being useful in the evaluation of postinjury nerve regeneration. This marker is not specific for regenerated filaments, but does represent a useful tool in the evaluation of nervous dynamic regeneration. The use of NFAP was reported in several studies, and was regarded as a quantitative marker for the rapidity of nerve regeneration in an inflammatory context (4), but also as an immunohistochemical 649 This article is freely accessible online.Correspondence to: Zorin Crăiniceanu,

Ovarian cancer remains one of the most aggressive and difficult to manage malignancies regarding evaluation and therapeutic options. The high mortality persists despite extensive research in the field. Current conventional chemotherapy does not improve disease-free survival and does not decrease recurrences amongst patients. This calls for a stringent reconsideration of the drugs selection, focused on the most targeted strategies and personalization of the therapy. Targeted agents against growth factors and their corresponding receptors are already approved as first- or second-line neoadjuvant therapy with controversial results. This chapter critically discusses the role of growth factors as vascular endothelial growth factor, fibroblast growth factors, or platelet-derived growth factors and their corresponding receptors in the pathogenesis, progression, and selection of therapeutic strategies. Other growth factors, such as nerve growth factor or endocrine gland derived growth factor, seem to have a strong involvement in ovarian carcinogenesis but their actual impact is not fully understood.