The expression of monocarboxylate transporters in thyroid carcinoma can be associated with the morphological features of BRAF (V600E) mutation

BRAF (V600E) mutation, usually performed by DNA techniques, is one of the most common diagnostic markers in papillary thyroid carcinoma. Few papers have demonstrated that plump cells (eosinophilic cytoplasms and papillary thyroid carcinoma nuclei) and peculiar sickle-shaped nuclei represent morphological features of BRAF (V600E) on papillary thyroid carcinomas. These features seem to be linked to glycolytic phenotype whereby monocarboxylate transporters 1-4 are hypothesized to have a dominant role as lactate transporters. We investigated the association between these morphological features and monocarboxylate transporters 1 and 4 in 48 cyto-histological samples diagnosed as "positive for malignancy-favoring papillary thyroid carcinoma". These cases were processed with liquid-based cytology and underwent BRAF (V600E) mutational analysis (pyrosequencing) on liquid-based cytology and monocarboxylate transporters immunostaining on histology. The expression of monocarboxylate transporter 1, monocarboxylate transporter 4, glucose trasporter-1 and carbonic anhidrase were scored semi-quantitatively with expression from 0 to 3+ (strong positivity). The 33 mutated and 15 wild type cases showed 100 % cyto-histological concordance. The cytological evaluation revealed plump cells and sickle nuclear shape in 100 % mutated cases. Monocarboxylate transporter 1 yielded 76 % positivity in the mutated cases especially in both the plump cells and sickle-shaped nuclei, whereas the wild types showed 13.3 % positive monocarboxylate transporter 1 (p = 0.00013). Monocarboxylate transporter 4 resulted in 100 % positivity in mutated and 40 % in wild types (p 0.05). This is the first report analyzing the association between monocarboxylate transporter expression and the morphological features of BRAF (V600E) mutated papillary thyroid carcinomas suggesting the possible involvement of lactate in the morphological features.info:eu-repo/semantics/publishedVersio

Street art cannot do redevelopment by itself

We often hear that street art can redevelop a neighborhood, especially during the election campaign by public administrations. Let’s say instead that street art cannot do redevelopment by itself but it is a first step to start virtuous processes, which if followed by interventions, in collaboration between public and private, aimed at arranging buildings, implementing services, creating local economies, so can certainly contribute to improving a periphery or a touristy depressed area and to change the perception of visitors for the better. The conversation with the artists wants to investigate: what is street art; what does it mean to paint on the walls, what is the message they want to communicate; what is their mission in art and if street art has the ability to redevelop a location. The dialogue consists in questions and the artists I selected are:Mauro Sgarbi: He was the creator of Street art for Amatrice, after the earthquake there, with the Up2Artists Association and other artists friends. Moby Dick: an artist who has always been involved in environmental issues, who with his works draws attention to animal species, espe-cially endangered ones.Solo: He partecipated with other artists to Re_Acto Fest in Paganica, a project by Luca Ximenes, in or-der to bring back to life the small municipalities hit by the earthquake in the province of L’Aquila. Alessia Babrow: an artist who has been working for years on a humanitarian level with actions that aim to make people think about universal values, to increase the level of awareness in people.DOI : https://doi.org/10.20365/disegnarecon.24.2020.i2</p

An abnormal secretion of soluble mediators contributes to the hematopoietic-niche dysfunction in low-risk myelodysplastic syndrome

N

CALR mutations in patients with essential thrombocythemia diagnosed in childhood and adolescence.

After the recent discovery of various mutations of theCALRgene,,10% of adult patients with essential thrombocythemia (ET) orprimary myelofibrosis carry no identified molecular markers.1,2More rarely, ET may occur also in children and adolescents.3Weevaluated, by Sanger sequencing, the mutation status of exon 9 oftheCALRgene in 34 ET patients younger than 20 years of age atdiagnosis (median age, 15 years; range, 1-19 years). The study wasapproved by the Institutional Ethic Committee

Well-differentiated Thyroid Cancer With a Minor Poorly Differentiated Component: Clonal Heterogeneity Through the Prognostic Role of CXCR4 and BRAF Analysis

Well-differentiated carcinoma (WDC) accounts for up to 90% of all thyroid cancers. The presence of a minor poorly differentiated (PD) component (mainly insular pattern) might represent an additional critical parameter for patients' prognosis and outcome. The role of both CXCR4 (a chemokine inducing cytoskeletal rearrangement and cell adhesion) and BRAF mutation have been studied in WDC (mainly papillary thyroid cancer and its variants), highlighting their critical role in tumor progression, local infiltration, and metastases. We discussed the clonal heterogeneity through the prognostic role of CXCR4 and BRAF mutation in WDC with a minor PD/insular component. Of our 16 WDC cases with a PD/insular component, up to 40% underwent surgery. The cases were subclassified according to the PD percentage as (1) <20% PD and (2) 20% to 40% PD, and were studied for CXCR4 expression and BRAF mutation. CXCR4 and molecular testing were distinctly performed on both components of each lesion. The majority of the cases (69%) showed an extrathyroid and metastatic dissemination. Regardless of the 2 categories, we had 8/16 (50%) patients with disease-free status. CXCR4 was negative in all 16 cases, whereas 3 of them (19%) had a mutated BRAF only in the WDC component of the lesion. WDCs with a minor PD pattern, even when <20%, showed more aggressive features than pure WDCs and should be entirely considered as PD carcinoma. The absence of CXCR4 expression and BRAF mutation in cancers with a minor PD component underlined different pathogenic and metastatic processes in comparison with WDCs

The mutant JAK2(V617F) allele burden in children with essential thrombocythemia

Children with ET, as adults, exhibit lower amounts of mutant alleles than children with PVET in childhood is characterized by lower mutant allelic burden than adults

Primary Trombocythemia in Children and Adolescents Includes Different Subtypes Compared to Adult Essential Thrombocythemia

The recent discovery of various mutations of the CALR gene that are mutually exclusive with JAK2 and MPL mutations has allowed a correct diagnosis in about 90% of adult cases of essential thrombocythemia (ET). Moreover, the mutation status of JAK2 and CARL defines subtypes of ET in adults with a substantially different clinical course and outcome. Based on our experience, we suggested that primary thrombocythemia (PT) in children is characterized by subtypes that differ from those found in adult ET. The present study was carried out in children and adolescents with PT in order to (a) characterize the various subtypes of the disease and (b) analyze their clinical and biologic features, treatment approach and outcome. PT patients aged &lt;20 years (yrs) at diagnosis (dx) were evaluated for mutations of JAK2, thrombopoietin (TPO) and its receptor (MPL) and CALR genes, and for clonal hematopoiesis (females). The presence of MPLS505A (confirmed on DNA from buccal swabs) defined a hereditary thrombocytosis (HT). ET was diagnosed according to WHO 2008 criteria. For wild type patients, an additional inclusion criteria was a follow-up &gt;24 months. Among 58 PT patients (males: 23; females: 35; median age at dx: 14.4 yrs), 21 (36%) had HT due to MPLS505A, 14 were JAK2V617F-mutated (24%), 9 (16%) harbored CALR mutations and 14 (24%) were wild type for JAK2, CALR and MPL (Fig 1). JAK2- and CALR-mutated were older than those with wild type ET or with HT (median age, 17.6 and 16.1 vs 10.4 and 13.7 yrs, p .028). As to the hematologic findings, HT patients showed both hematocrit values (median, 36.3%) and leukocytes counts (median, 9.53 x109/L) significantly lower than ET patients, whatever the subtypes (median, 41.2% and 11.2 x109/L, p .006 and p .029, respectively). No differences were found with regard to platelets both between HT and ET and among the different ET subtypes. JAK2-mutated patients exhibited more frequently symptoms (69%) compared to CALR-mutated (22%), wild-type ET (14%) and HT (14%) patients (p. 0057). Splenomegaly at diagnosis was recorded more frequently in JAK2-mutated than in CALR-mutated or wild type-ET or HT (50%, 33% 21% and 14% , respectively, p .122). Antiplatelet agents, mostly acetylsalicylic acid (ASA), were started less frequently in HT than in ET patients, irrespective of the subtypes (57% vs 81%, p .05). The use of ASA progressively decreased over the time; at the last follow-up, 2 patients with HT, 2 CALR-mutated and 1 JAK2-mutated patients were still receiving ASA, while no wild type ET patient was on treatment. Cytoreductive agents, hydroxyurea and/or interferon and/or anagrelide, were used in a minority of HT patients (19%) in comparison with ET patients (65%), p .001, mainly with those wild-type (78%, p &lt;.001). At the last observation, one HT patient was still receiving cytoreductive agents compared to 30% of ET patients whatever the subtypes (p .024). After a median follow-up of 196 months (similar in the different subtypes), all patients are alive. On the whole, 5 thrombotic events were recorded in 3 patients with HT and in 2 ET patients (1 JAK2-mutated and 1 JAK2 and CALR wild-type), without any significant thrombophilic abnormalities during treatment with ASA and/or cytoreductive agents. A progressive splenomegaly was recorded in 9 (15%) patients (2 HT, 4 JAK2-mutated, 3 CALR-mutated) and it was combined with grade ≥2 medullar fibrosis in 2/4 JAK2-mutated and in 2/3 CALR-mutated patients. None of the JAK2 and CALR wild-type patients had spleen enlargement or reticulin fibrosis (p .022). Two untreated patients (1 HT and JAK2 and CALR wild-type) developed malignancies. On the whole, these data emphasize that in young patients with PT, hereditary forms can be frequently observed. Thrombotic events, recorded mainly in HT patients despite treatment with ASA, were probably due to a MRP4 protein overexpression that was found in our MPLS505A HT. Moreover, our observations highlight that, in contrast to adult ET, more than one third of young ET patients have no JAK2 or CALR mutations

Endothelial Progenitor Cell Dysfunction in Myelodysplastic Syndromes: Possible Contribution of a Defective Vascular Niche to Myelodysplasia

We set a model to replicate the vascular bone marrow niche by using endothelial colony forming cells (ECFCs), and we used it to explore the vascular niche function in patients with low-risk myelodysplastic syndromes (MDS). Overall, we investigated 56 patients and we observed higher levels of ECFCs in MDS than in healthy controls; moreover, MDS ECFCs were found variably hypermethylated for p15INK4b DAPK1, CDH1, or SOCS1. MDS ECFCs exhibited a marked adhesive capacity to normal mononuclear cells. When normal CD34+ cells were co-cultured with MDS ECFCs, they generated significant lower amounts of CD11b+ and CD41+ cells than in co-culture with normal ECFCs. At gene expression profile, several genes involved in cell adhesion were upregulated in MDS ECFCs, while several members of the Wingless and int (Wnt) pathways were underexpressed. Furthermore, at miRNA expression profile, MDS ECFCs hypo-expressed various miRNAs involved in Wnt pathway regulation. The addition of Wnt3A reduced the expression of intercellular cell adhesion molecule-1 on MDS ECFCs and restored the defective expression of markers of differentiation. Overall, our data demonstrate that in low-risk MDS, ECFCs exhibit various primary abnormalities, including putative MDS signatures, and suggest the possible contribution of the vascular niche dysfunction to myelodysplasia