In stage II/III lymph node positive breast cancer patients less than 55 years of age, keratin 8 expression in lymph node metastases but not in the primary tumor is an indicator of better survival

Axillary lymph node status is one of the most important prognostic variables for breast cancer (BC). To investigate and understand the clinical, histopathological and biological factors that affect prognosis in node positive young breast cancer patients, we compared the phenotype of 100 primary tumours with their corresponding loco- regional lymph node (LN) metastases using conventional immunohistochemistry (IHC) markers currently in use for molecular classification of breast cancer. By comparing the expression of ER, PR, HER-2, Ki67, K8, K5/6 and vimentin, we found that expression of HER-2, Ki67, K8 and vimentin is frequently lost in lymph node metastases. Between the primary tumour and corresponding lymph node metastases expression of keratins K8 and K5/6 significantly changed. Expression of K8 in lymph node metastases, but not in primary tumours, segregates patients in two sub-groups with different outcome. Survival of patients with K8 positive LN metastases at 5 years in comparison with patients with K8 negative LN metastases was 75% vs 48%, at 10 years 62% vs 22% and at 20 years 53% vs 14%(p<0.001). K8 immunostaining of tissue from the lymph node metastasis allows defining a sub-group of lymph node positive BC patients with a highly unfavourable outcome, for whom therapeutic options might have to be reconsidered

PI3K/AKT Signaling in Breast Cancer Molecular Subtyping and Lymph Node Involvement

Lymph node metastatic involvement persists to be among the most important predictors of recurrence and survival in breast carcinoma (BC). This study aimed at investigating possible gene expression differences in primary BC between patients with or without lymph node involvement at the time of diagnosis. In a retrospective study, we investigated the potential prognostic role of 9 candidate biomarkers at mRNA level in a cohort of 305 breast cancer patients, 151 lymph node-negative (LN-) and 154 lymph node-positive (LN+). The analyzed genes belonged to the RAS pathway (RAF1, ERBB2, PIK3CB, AKT1, AKT2, AKT3), RB pathway (RB1 and CDK2) and cellular differentiation (KTR8). Their expression profiles were investigated by RT-qPCR and were correlated to immunohistochemically-based molecular subtypes and BC clinical and pathological features. The differential expression of several genes in the primary tumor tissue was related to the LN involvement. Some of those genes, including PIK3CB, RB1, and AKT3, were more expressed in LN- BC patients, while some others, notably ERBB2 and AKT1, in LN+ ones. Among the candidate biomarkers, the expression levels of AKTs isoforms influenced also patients\u2019 survival rates. In detail, higher expression levels of AKT1 and AKT2 negatively influenced overall patients\u2019 survival and in particular AKT2 expression levels defined a group of luminal B BC patients with shorter cancer-specific survival. On the contrary, longer cancer-specific survival was recorded in luminal A BC patients with higher expression levels of AKT3. That finding was also confirmed by Cox multivariate analysis. The same AKT3 resulted to be a possible candidate predictive biomarker for Tamoxifen response. In conclusion, our study highlighted the complex regulation of the PI3K/AKT pathway in BC and its differences in BC patients with and without lymph node involvement

po 349 akt3 but not akt1 and akt2 confers a longer survival rate to less aggressive breast cancers

Introduction Breast carcinoma (BC) encompasses a heterogeneous group of tumours with a great variability at the molecular and morphological levels and clinical outcome. Material and methods In this retrospective study we investigated the potential prognostic role of 9 candidate biomarkers in a cohort of 305 breast cancer (BC) patients, both lymph node negative (151) and lymph node positive (154). The analysed genes belonged to the RAS pathway (RAF1, ERBB2, PIK3B, AKT1, AKT2, AKT3), RB pathway (RB1 and CDK2) and cellular differentiation (K8). The expression profiles were investigated by real-time qPCR in formalin-fixed and paraffin-embedded tissues, and correlated to immunohistochemical-based molecular classes, namely luminal A, luminal B, Her2 +and TN. The study was approved by the Ethical Committee of the University of Trieste. Results and discussions In our cohort lymph node involvement resulted to be related to the contribution of several genes at the primary tumour tissue level. Some of those genes resulted to be more expressed in LN negative BC, such as PIK3B, RB1 and AKT3, while some others were more expressed in LN positive BC, such as HER2 and AKT1. Our results show higher expression levels of PIK3B and AKT3 in less aggressive BC and higher expression levels of AKT1 in more aggressive BC highlighting the complex regulation of that pathway in BC. Shorter cancer specific survival was recorded in patients expressing higher levels of AKT1 and AKT2. Furthermore, better cancer specific survival was recorded in luminal A BC patients expressing higher levels of AKT3 (p=0.005 in LN- and p=0.01 in LN+). Conclusion By comparing gene expression in lymph node negative and lymph node positive breast cancers, we found that AKT3 is an independent favourable prognostic factor for luminal A BC patients. Our results showed that a high expression level of AKT3, but not AKT1 and AKT2 was associated to better outcome and longer cancer specific patients' survival in those patients who display the luminal A molecular class irrespective of lymph node involvement

Nucleation and crystallization in bio-based immiscible polyester blends

Bio-based thermoplastic polyesters are highly promising materials as they combine interesting thermal and physical properties and in many cases biodegradability. However, sometimes the best property balance can only be achieved by blending in order to improve barrier properties, biodegradability or mechanical properties. Nucleation, crystallization and morphology are key factors that can dominate all these properties in crystallizable biobased polyesters. Therefore, their understanding, prediction and tailoring is essential. In this work, after a brief introduction about immiscible polymer blends, we summarize the crystallization behavior of the most important bio-based (and immiscible) polyester blends, considering examples of double-crystalline components. Even though in some specific blends (e.g., polylactide/polycaprolactone) many efforts have been made to understand the influence of blending on the nucleation, crystallization and morphology of the parent components, there are still many points that have yet to be understood. In the case of other immiscible polyester blends systems, the literature is scarce, opening up opportunities in this environmentally important research topic.The authors would like to acknowledge funding by the BIODEST project ((RISE) H2020-MSCA-RISE-2017-778092

Filler Toughening of Plastics. Part 1 - The Effect of Surface Interactions on Physico-Mechanical Properties and Rheological Behaviour of Ultrafine CaCO3/High Density Polyethylene Nanocomposites

Precipitated CaCO3 (PCC)/High Density Polyethylene (HDPE) composites were prepared on a twin screw mixer-single screw extruder with a particle content of 10 vol%. The average particle size was 70 nm. The influence of surface treatment of the particles, with and without stearic acid (SA), on the physico-mechanical and rheological properties was studied. The experiments included tensile tests, impact tests, differential scanning calorimetry (DSC), microscopy and rheology experiments. The addition of 10 vol% calcium carbonate to HDPE causes a rise in Young's modulus and yield stress of its composites and is accompanied by a sharp drop in impact strength. The addition of SA has the effect of slightly decreasing both Young's modulus and yield stress of the composites compared to the uncoated PCC composites, while the impact strength progressively increases. During the tensile test filled HDPE composites showed stress whitening zones appear and develop along the gauge length. Volume measurements during tensile tests showed an increase in volume strain with deformation, due to the matrix-particle debonding phenomenon, while pure HDPE showed actually a decrease in volume with elongation. At constant deformation, for the composites with coated PCC, it can be observed that an increase in the SA content leads to a slight decrease in volume change. The microscopical evaluation showed cavities and voids due to debonding and deformation bands in the stress whitened areas. DSC experiments have shown that uncoated PCC particles have a very small nucleating effect on HDPE

STRUCTURE PROPERTY RELATIONSHIPS OF POLYMER BLENDS BASED ON FUNCTIONALIZED POLYOLEFINS

The thermal behaviour, morphology, molecular interactions and phase structure of blends based on polyolefins functionalised with diethylmaleate and commercial polymers (poly(vinyl chloride), polystyrene, poly(vinyliden fluoride)) were analysed by means of DSC, FT-IR, optical and electron microscopy. It is shown that the occurrence of partial miscibility phenomena is favoured by specific molecular interactions between the polymer components and is affected by the structure of the functionalised polyolefins, degree of functionalisation and thermal history