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

Effect of chemical treatment on the mechanical and thermal properties of hemp fibre reinforced thermoset sandwich composites

In this study hemp-thermoset sandwich composites were prepared by using unsaturated polyester resin. To improve fibre matrix adhesion alkalization and acetylation treatment on the fibres were carried out. Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) were used to investigate the changes of fibres chemical constituents after treatment. Mechanical properties such as flexural strength, flexural modulus and strain at break of untreated and treated fibre composites were studied and compared. The incorporation of the alkalized fibres resulted in composites better flexural properties and 8% treatment showed best results. Thermal stability of the fibre was also enhanced for the treated fibre. In general, thermal and mechanical properties of the treated fibre and its composites were superior to the untreated fibres