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Antipituitary antibodies (APA) but not antihypothalamus antibodies (AHA) are usually searched for in autoimmune hypopituitarism.Our objective was to search for AHA and characterize their hypothalamic target in patients with autoimmune hypopituitarism to clarify, on the basis of the cells stained by these antibodies, the occurrence of autoimmune subclinical/clinical central diabetes insipidus (CDI) and/or possible joint hypothalamic contribution to their hypopituitarism.We conducted a cross-sectional cohort study.Ninety-five APA-positive patients with autoimmune hypopituitarism, 60 without (group 1) and 35 with (group 2) lymphocytic hypophysitis, were studied in comparison with 20 patients with postsurgical hypopituitarism and 50 normal subjects.AHA by immunofluorescence and posterior pituitary function were evaluated; then AHA-positive sera were retested by double immunofluorescence to identify the hypothalamic cells targeted by AHA.AHA were detected at high titer in 12 patients in group 1 and in eight patients in group 2. They immunostained arginine vasopressin (AVP)-secreting cells in nine of 12 in group 1 and in four of eight in group 2. All AVP cell antibody-positive patients presented with subclinical/clinical CDI; in contrast, four patients with GH/ACTH deficiency but with APA staining only GH-secreting cells showed AHA targeting CRH- secreting cells.The occurrence of CDI in patients with lymphocytic hypophysitis seems due to an autoimmune hypothalamic involvement rather than an expansion of the pituitary inflammatory process. To search for AVP antibody in these patients may help to identify those of them prone to develop an autoimmune CDI. The detection of AHA targeting CRH-secreting cells in some patients with GH/ACTH deficiency but with APA targeting only GH-secreting cells indicates that an autoimmune aggression to hypothalamus is jointly responsible for their hypopituitarism.

OBJECTIVE: Antipituitary (APA) but not antihypothalamus antibodies (AHA) have been investigated in patients with idiopathic hypopituitarism. This study searched for APA and AHA in some of these patients to investigate whether pituitary or hypothalamic autoimmunity could play a role in their pituitary dysfunction. DESIGN: Sixty-six patients with selective idiopathic hypopituitarism were studied: 27 with ACTH deficiency, 20 with GH deficiency and 19 with hypogonadotropic hypogonadism. Twenty patients with hypopituitarism secondary to hypophysectomy and 50 healthy subjects were enrolled as controls. MEASUREMENTS: Antipituitary and AHA were evaluated by indirect immunofluorescence in sera of patients and controls. Positive sera were retested by a four-layer double immunofluorescence to identify the cells targeted by these antibodies. RESULTS: Antipituitary were present at high titre in 4 of 27 patients with ACTH deficiency (14·8%), 4 of 20 with GH deficiency (26%) and 5 of 19 with hypogonadotropic hypogonadism (21%) and targeted, respectively, corticotrophs, somatotrophs and gonadotrophs. AHA were found at high titre only in 5 patients with ACTH deficiency (18·5%), mostly targeting corticotrophin-releasing hormone-secreting cells; none of these 5 patients resulted positive for antipituitary antibodies. Among the controls, only 1 hypophysectomized patient resulted APA positive at low titre. CONCLUSIONS: Our results suggest that in patients with selective idiopathic hypopituitarism, detection of APA or AHA could better characterize an autoimmune process involving the pituitary or hypothalamus, respectively. In particular, detection of antibodies targeting selectively ACTH-secreting or corticotrophin-releasing hormone-secreting cells may differentiate, respectively secondary from tertiary variants of autoimmune hypoadrenalism

CONTEXT: Antipituitary antibodies (APA) are frequently present in patients with autoimmune polyendocrine syndrome (APS). DESIGN: The aim was to evaluate the predictive value of APA for the occurrence of hypopituitarism. A total of 149 APA-positive and 50 APA-negative patients with APS and normal pituitary function were longitudinally studied for 5 yr. METHODS: APA, by indirect immunofluorescence, and anterior pituitary function were assessed yearly in all patients. The risk for developing autoimmune pituitary dysfunction was calculated using survival and multivariate analysis. RESULTS: Hypopituitarism occurred in 28 of 149 (18.8%) APA-positive patients but in none of the 50 APA-negative patients. The immunostaining pattern in APA-positive patients involved either isolated pituitary cells [type 1 pattern; n=99 (66.4%)] or all pituitary cells [type 2 pattern; n=50 (33.6%)]. All patients developing pituitary dysfunction throughout the study span had a type 1 pattern. Kaplan-Meier curves for cumulative survival showed a significantly higher rate for developing hypopituitarism in relation to positive APA tests (P

Distinguishing Burkitt lymphoma (BL) from B cell lymphoma, unclassifiable with features intermediate between diffuse large B-cell lymphoma (DLBCL) and BL (DLBCL/BL), and DLBCL is challenging. We propose an immunohistochemistry and fluorescent in situ hybridization (FISH) based scoring system that is employed in three phases - Phase 1 (morphology with CD10 and BCL2 immunostains), Phase 2 (CD38, CD44 and Ki-67 immunostains) and Phase 3 (FISH on paraffin sections for MYC, BCL2, BCL6 and immunoglobulin family genes). The system was evaluated on 252 aggressive B-cell lymphomas from Europe and from sub-Saharan Africa. Using the algorithm, we determined a specific diagnosis of BL or not-BL in 82%, 92% and 95% cases at Phases 1, 2 and 3, respectively. In 3·4% cases, the algorithm was not completely applicable due to technical reasons. Overall, this approach led to a specific diagnosis of BL in 122 cases and to a specific diagnosis of either DLBCL or DLBCL/BL in 94% of cases that were not diagnosed as BL. We also evaluated the scoring system on 27 cases of BL confirmed on gene expression/microRNA expression profiling. Phase 1 of our scoring system led to a diagnosis of BL in 100% of these cases.

Everolimus is a valid therapeutic option for neuroendocrine tumors (NETs); however, data in a real-world setting outside regulatory trials are sparse. The aim of this study was to determine everolimus tolerability and efficacy, in relation to previous treatments, in a compassionate use program. A total of 169 patients with advanced progressive NETs treated with everolimus were enrolled, including 85 with pancreatic NETs (pNETs) and 84 with nonpancreatic NETs (non-pNETs). Previous treatments included somatostatin analogs (92.9%), peptide receptor radionuclide therapy (PRRT; 50.3%), chemotherapy (49.7%), and PRRT and chemotherapy (22.8%). Overall, 85.2% of patients experienced adverse events (AEs), which were severe (grade 3–4) in 46.1%. The most frequent severe AEs were pneumonitis (8.3%), thrombocytopenia (7.7%), anemia (5.3%), and renal failure (3.5%). In patients previously treated with PRRT and chemotherapy, a 12-fold increased risk for severe toxicity was observed, with grade 3–4 AEs reported in 86.8% (vs. 34.3% in other patients). In addition, 63.3% of patients required temporarily everolimus discontinuation due to toxicity. Overall, 27.8% of patients died during a median follow-up of 12 months. Median progression-free survival (PFS) and overall survival (OS) were 12 months and 32 months, respectively. Similar disease control rates, PFS, and OS were reported in pNETs and non-pNETs. In the real-world setting, everolimus is safe and effective for the treatment of NETs of different origins. Higher severe toxicity occurred in patients previously treated with systemic chemotherapy and PRRT. This finding prompts caution when using this drug in pretreated patients and raises the issue of planning for everolimus before PRRT and chemotherapy in the therapeutic algorithm for advanced NETs.

BACKGROUND: Recent evidence suggests that lipid pathway is altered in many human tumours. In Burkitt lymphoma this is reflected by the presence of lipid droplets which are visible in the cytoplasm of neoplastic cells in cytological preparations. These vacuoles are not identifiable in biopsy section as lipids are "lost" during tissue processing. METHODS AND RESULTS: In this study we investigated the expression of genes involved in lipid metabolism, at both RNA and protein level in Burkitt lymphoma and in other B-cell aggressive lymphoma cases. Gene expression profile indicated a significant over-expression of the adipophilin gene and marked up-regulation of other genes involved in lipid metabolism in Burkitt lymphoma. These findings were confirmed by immunohistochemistry on a series od additional histological samples: 45 out of 47 BL cases showed strong adipophilin expression, while only 3 cases of the 33 of the not-Burkitt lymphoma category showed weak adipophilin expression (p

Adipose tissue‐derived mesenchymal stem cells (Ad‐MSC) and platelet derivatives have been used alone or in combination to achieve regeneration of injured tissues. We have tested the effect of platelet‐rich plasma (PRP) on Ad‐MSC and adipocyte function. PRP increased Ad‐MSC viability, proliferation rate and G1‐S cell cycle progression, by at least 7‐, 2‐, and 2.2‐fold, respectively, and reduced caspase 3 cleavage. Higher PRP concentrations or PRPs derived from individuals with higher platelet counts were more effective in increasing Ad‐MSC growth. PRP also accelerated cell migration by at least 1.5‐fold. However, PRP did not significantly affect mature adipocyte viability, differentiation and expression levels of PPAR‐γ and AP‐2 mRNAs, while it increased leptin production by 3.5‐fold. Interestingly, PRP treatment of mature adipocytes also enhanced the release of Interleukin (IL)‐6, IL‐8, IL‐10, Interferon‐γ, and Vascular Endothelial Growth Factor. Thus, data are consistent with a stimulatory effect of platelet derivatives on Ad‐MSC growth and motility. Moreover, PRP did not reduce mature adipocyte survival and increased the release of pro‐angiogenic factors, which may facilitate tissue regeneration processes. © 2015 The Authors. Journal of Cellular Biochemistry Published by Wiley Periodicals, Inc. J. Cell. Biochem. 116: 2408–2418, 2015. © 2015 The Authors. Journal of Cellular Biochemistry Published by Wiley Periodicals, Inc.

In this paper we propose polysaccharide hydrogels combining alginate (ALG) and hyaluronan (HA) as biofunctional platform for dermal wound repair. Hydrogels produced by internal gelation were homogeneous and easy to handle. Rheological evaluation of gelation kinetics of ALG/HA mixtures at different ratios allowed understanding the HA effect on ALG cross-linking process. Disk-shaped hydrogels, at different ALG/HA ratio, were characterized for morphology, homogeneity and mechanical properties. Results suggest that, although the presence of HA does significantly slow down gelation kinetics, the concentration of cross-links reached at the end of gelation is scarcely affected. The in vitro activity of ALG/HA dressings was tested on adipose derived multipotent adult stem cells (Ad-MSC) and an immortalized keratinocyte cell line (HaCaT). Hydrogels did not interfere with cell viability in both cells lines, but significantly promoted gap closure in a scratch assay at early (1 day) and late (5 days) stages as compared to hydrogels made of ALG alone (p < 0.01 and 0.001 for Ad-MSC and HaCaT, respectively). In vivo wound healing studies, conducted on a rat model of excised wound indicated that after 5 days ALG/HA hydrogels significantly promoted wound closure as compared to ALG ones (p < 0.001). Overall results demonstrate that the integration of HA in a physically cross-linked ALG hydrogel can be a versatile strategy to promote wound healing that can be easily translated in a clinical setting.

Chronic growth hormone (GH)/insulin-like growth factor I (IGF-I) excess is associated with considerable mortality in acromegaly, but no data are available in pituitary gigantism. The aim of the study was to evaluate the long-term effects of early exposure to GH and IGF-I excess on cardiovascular and metabolic parameters in adult patients with pituitary gigantism. Six adult male patients with newly diagnosed gigantism due to GH secreting pituitary adenoma were studied and compared with 6 age- and sex-matched patients with acromegaly and 10 healthy subjects. Morphologic and functional cardiac parameters were evaluated by Doppler echocardiography. Glucose metabolism was assessed by evaluating glucose tolerance and homeostasis model assessment index. Disease duration was significantly longer (P < .05) in patients with gigantism than in patients with acromegaly, whereas GH and IGF-I concentrations were comparable. Left ventricular mass was increased both in patients with gigantism and in patients with acromegaly, as compared with controls. Left ventricular hypertrophy was detected in 2 of 6 of both patients with gigantism and patients with acromegaly, and isolated intraventricular septum thickening in 1 patient with gigantism. Inadequate diastolic filling (ratio between early and late transmitral flow velocity

Acromegaly management is a significant challenge for endocrinologists. The Acromegaly Consensus Group developed several statements on the management of acromegaly and specifically on its medical treatment [1–3]. Acromegaly is a quite rare condition generally caused by a growth hormone (GH)-secreting pituitary adenoma [4]. Delayed diagnosis leads to prevalent presentation of the disease at the stage of macroadenoma (two-thirds of patients) and frequent persistence of active disease after surgery which remains in many patients the primary treatment option [5]. However, active acromegaly is potentially a life threatening condition due its severe systemic complications [6, 7] Therefore, elevated GH and insulin-like growth factor (IGF)-1 levels need to be strictly controlled after failure of surgery with medical or radiation treatments [8]. Furthermore, criteria for disease control may not be fulfilled in a considerable proportion of patients undergoing medical treatment with somatostatin receptor ligands (SRLs) after unsuccessful surgery [9, 10]. Accordingly, some acromegaly patients require the administration of GH antagonist Pegvisomant [11]. Pegvisomant has been introduced in clinical practice more than a decade ago as a medical therapy of acromegaly. However, specific guidelines for Pegvisomant use in acromegaly are lacking. Therefore, the Italian Society of Endocrinology constituted a task force with the objective of assessing the published literature and the clinical experience with Pegvisomant. This group involved endocrinologists recognized experts in the field of acromegaly management and their understanding of the data reported so far worldwide as well as their recommendations for Pegvisomant use in clinical practice are presented here. Biochemical and clinical results of Pegvisomant, indications, treatment modalities, combination therapies, safety and regulatory and cost/efficacy issues were evaluated. Evidences were graded with GRADE system [1–3, 12, 13] based on the quality of evidence as very low quality (VLQ; expert opinion with one or a small number of small uncontrolled studies in support), low quality (LQ; large series of small uncontrolled studies), moderate quality (MQ; one or a small number of large uncontrolled studies or meta-analyses), or high quality (HQ; controlled studies or large series of large uncontrolled studies with sufficiently long follow-up). Recommendations were defined discretionary (DR) if based on VLQ-LQ evidence, or strong (SR) if supported by MQ-HQ evidence.

Glomus tumors are rare, mesenchymal neoplasms of adulthood, which occur in both the sexes with equal frequency. Most of these tumors are benign, but some cases with atypical/malignant behavior have been reported. They most often occur in the extremities, typically in the subungual region of the fingers, and rarely involve the internal organs. We report the case of a 63-year-old man who presented with hematuria. The cystoscopy showed a polypoid lesion of the anterior wall of the bladder, which was diagnosed on biopsy as a benign glomus tumor. To the best of our knowledge, this is the first case of benign glomus tumor of the bladder described in the literature. This report widens the spectrum of the differential diagnoses of bladder neoplasms.

Background: During the course of acromegaly, cardiovascular, respiratory, and metabolic co-morbidities contribute to enhanced mortality. In 2002, the Pituitary Society and the European Neuroendocrine Association sponsored a Consensus Workshop in Versailles during which guidelines for diagnosis and treatment of co-morbidities in acromegaly were defined. However, as for other guidelines previously issued in the field, no data are available on their clinical application. Aim: The aim of this work coordinated by the Italian Study group on co-morbidities evaluation and treatment in acromegaly (COM.E.T.A.) was to assess, on a national basis, the application in the clinical practice of the Versailles criteria for diagnosis and treatment of cardiovascular comorbities in acromegaly. Materials and methods: In January 2007 an ad hoc designed questionnaire was sent by mail to 130 endocrine Centers in Italy. Results: The guidelines have been generally well perceived and translated in clinical practice. Specifically: 1) echocardiography is considered the mainstay for the diagnosis and follow-up; 2) ambulatory blood pressure monitoring and blood lipid assessment are performed in most hypertensive patients; 3) most endocrinologists directly manage hypertension and are aware of the uncertainty of the effect of the control of the disease on blood pressure levels; 4) ACE inhibitors and angiotensin receptors blockers are first-choice anti-hypertensive treatment; 5) approximately half of the centers consider somatostatin analogues of paramount relevance for biochemical control of disease; 6) awareness that left ventricular hypertrophy and heart failure are the most relevant cardiovascular complications is high although the impact of ischemic, arrhythmic, and valvular complications on prognosis is less well perceived. Conclusion: The results of the present survey suggest that previuosly issued guidelines are generally carefully followed in the clinical practice. On the other side, a certain lack of awareness of emerging aspects of the cardiovascular comorbities of acromegaly confirms the necessity of periodically updating the guidelines based on the availability of new clinical information.

Ki-67 is a marker of proliferation activity associated with invasiveness and prognosis in human tumors.The aim of the study was to evaluate the Ki-67 index prognostic relevance in a group of acromegalic patients who underwent transsphenoidal surgery for a GH-secreting pituitary adenoma.We selected 68 consecutive acromegalic patients referred to our hospital during a 5-yr period. The Ki-67 index was determined by immunohistochemistry on tissue samples obtained from each adenoma after surgery. Those patients who were not completely cured after surgery began medical therapy with somatostatin analogs (SSAs). Periodical pituitary magnetic resonance imaging and hormonal evaluation were performed during the follow-up.Twenty-eight of 68 patients were cured after surgery (41%). Among the 40 patients treated with SSAs, 13 were considered uncontrolled. Pituitary magnetic resonance imaging showed residual/recurrent disease in 25 of 68 patients after 6 months. No correlation was found between Ki-67 index and age, tumor size, GH, or IGF-I plasma levels. Tumors described as having cavernous sinus invasion had a higher mean Ki-67 index as compared with noninvasive tumors (P0.01). The Ki-67 index was significantly lower in tumors in patients cured after surgery as compared with patients considered not cured (P0.01) and in tumors in patients controlled by SSA therapy as compared with patients considered as uncontrolled (P0.05).The Ki-67 labeling index may predict clinical outcome in postsurgical management of acromegalic patients. We suggest routine Ki-67 evaluation in GH-secreting pituitary adenomas.

Recently, a new slow-release (SR) formulation of lanreotide (LAN) comprising 60 mg of the drug incorporated in microspheres of biodegradable polymers (SR-LAN 60) has become available. The aim of our study was to assess the effectiveness of SR-LAN 60, administered every 21 to 28 days, as well as its tolerability in the long-term treatment of acromegalic patients treated with SR-LAN 30. Twenty patients with acromegaly (10 males and 10 females) were enrolled in this open study. Thirteen patients had undergone surgery, but with incomplete resection of the pituitary tumor. All patients, treated with intramuscular (IM) SR-LAN 30 injections every 10 days for 12 to 24 months, started SR-LAN 60 (Ipsen-Beaufour, Milan, Italy) administration 10 days after the last injection of SR-LAN 30. Growth hormone (GH) levels were determined on the day of the first injection of SR-LAN 60, and 10, 20, and 30 days after. According to the GH levels reached on day 30, patients received SR-LAN 60 every 28 days if GH levels were below 2.5 microg/L (group A) and every 21 days if GH levels were above 2.5 microg/L (group B). In group A, after the 8th month, SR-LAN 60 treatment resulted in well-controlled GH levels in 9 of 10 patients in comparison to SR-LAN 30 treatment every 10 days (6 of 10 patients). Normal age-adjusted insulin-like growth factor-I (IGF-I) levels were achieved in 4 of 10 patients, as in treatment with SR-LAN 30. In group B, SR-LAN 60 treatment resulted in well-controlled GH levels in 4 of 10 patients, as in treatment with SR-LAN 30 every 10 days. Normal age-adjusted IGF-I levels were achieved in 3 of 10 patients after SR-LAN 60 in comparison to SR-LAN 30 treatment every 10 days (1 of 10 patients). During SR-LAN 60 therapy, an improvement was also observed in signs and symptoms of active acromegaly and no relevant side effects were detected. In conclusion, this study shows that SR-LAN 60 treatment is able to induce a good control of circulating GH and IGF-I levels in most acromegalic patients. The first injections of SR-LAN 60 are very helpful in predicting the optimal long-term injection frequency. Patients on SR-LAN 30 can be safely and effectively shifted to SR-LAN 60.

A substantial proportion of GH circulates bound to high affinity GH-binding protein (GHBP), which corresponds to the extracellular domain of the GH receptor. Current evidence indicates that nutritional status has an important role in regulating plasma GHBP levels in humans. In the present study the relationship among plasma GHBP levels, body composition [by bioelectrical impedance analysis (BIA) and dual energy x-ray absorptiometry (DEXA)] and serum estradiol (E2) was evaluated in premenopausal (n 5 92) and postmenopausal (n 5 118) healthy women with different body weight [three groups according to body mass index (BMI): normal, 18.5–24.99; overweight, 25–29.99; obese, 30–39.99 kg/m2]. Plasma GHBP levels were measured by high pressure liquid chromatography gel filtration. GH and insulin-like growth factor I levels were determined by immunoradiometric assay and RIA, respectively. GHBP levels were significantly higher in premenopausal women with BMI above 25 kg/m2 (overweight, 3.789 6 0.306 nmol/L; obese, 4.37260.431 nmol/L) than those observed in postmenopausal women (overweight, 1.425 6 0.09 nmol/L; obese, 1.506 6 0.177 nmol/L). No significant differences were found between normal weight premenopausal (1.741 6 0.104 nmol/L) and postmenopausal (1.524 6 0.202 nmol/L) women. In premenopausal women GHBP levels correlated positively with BMI (r 5 0.675; P , 0.001), fat mass (FM; r 5 0.782; P , 0.001; by BIA; r 5 0.776; P , 0.001; by DEXA), truncal fat (TF; r 5 0.682; P , 0.001), waist to hip circumference ratio (WHR; r 5 0.551; P , 0.001), and E2 (r 5 0.298; P , 0.05), whereas no significant correlation was found in postmenopausal women between GHBP levels and BMI, FM, TF, WHR, or E2. In normal weight pre- and postmenopausal women GHBP levels did not change between the ages of 20 and 69 yr. No statistically significant correlation was found between GHBP and age for all groups studied. Moreover, in two distinct subgroups of pre- and postmenopausal women, aged 40–49 yr, the direct relationship between GHBP levels and all indexes of adiposity were only observed in premenopausal women [BMI: r 5 0.836; P , 0.001; FM: r 5 0.745 (BIA) and r 5 0.832 (DEXA); P , 0.001; TF: r 5 0.782; P , 0.001; WHR: r 5 0.551; P , 0.05], but not in postmenopausal women. In conclusion, the present data indicate a strong direct correlation between GHBP and body fat in premenopausal, but not in postmenopausal women, whereas they failed to detect a relationship between GHBP and age. Therefore, these results suggest that endogenous estrogen status may be an important determinant of the changes in GHBP levels in women with different body weights.

// Vittoria D'Esposito 1 , Domenico Liguoro 1 , Maria Rosaria Ambrosio 1 , Francesca Collina 2 , Monica Cantile 2 , Rosa Spinelli 1 , Gregory Alexander Raciti 1 , Claudia Miele 1 , Rossella Valentino 1 , Pietro Campiglia 3 , Michelino De Laurentiis 4 , Maurizio Di Bonito 2 , Gerardo Botti 2 , Renato Franco 2 , Francesco Beguinot 1 , Pietro Formisano 1 1 Department of Translational Medicine, Federico II University of Naples and URT “Genomic of Diabetes” of Institute of Experimental Endocrinology and Oncology, National Council of Research (CNR), Naples, Italy 2 Pathology Unit, National Institute of Tumors, Fondazione “G. Pascale”, Naples, Italy 3 Department of Pharmacy, University of Salerno, Salerno, Italy 4 Department of Breast Surgery and Cancer Prevention; National Institute of Tumors, Fondazione “G. Pascale”, Naples, Italy Correspondence to: Pietro Formisano, e-mail: fpietro@unina.it Keywords: triple negative breast cancer, adipose tissue, cytokines, diabetes, obesity Received: August 05, 2015 Accepted: February 28, 2016 Published: March 24, 2016 ABSTRACT Growing evidence indicates that adiposity is associated with raised cancer incidence, morbidity and mortality. In a subset of tumors, cancer cell growth and/or metastasis predominantly occur in adipocyte-rich microenvironment. Indeed, adipocytes represent the most abundant cell types surrounding breast cancer cells. We have studied the mechanisms by which peritumoral human adipose tissue contributes to Triple Negative Breast Cancer (TNBC) cell invasiveness and dissemination. Co-culture with human adipocytes enhanced MDA-MB231 cancer cell invasiveness. Adipocytes cultured in high glucose were 2-fold more active in promoting cell invasion and motility compared to those cultured in low glucose. This effect is induced, at least in part, by the CC-chemokine ligand 5 (CCL5). Indeed, CCL5 inhibition by specific peptides and antibodies reduced adipocyte-induced breast cancer cell migration and invasion. CCL5 immuno-detection in peritumoral adipose tissue of women with TNBC correlated with lymph node ( p -value = 0.04) and distant metastases ( p -value = 0.001). A positive trend was also observed between CCL5 expression and glycaemia. Finally, Kaplan-Meier curves showed a negative correlation between CCL5 staining in the peritumoral adipose tissue and overall survival of patients ( p -value = 0.039). Thus, inhibition of CCL5 in adipose microenvironment may represent a novel approach for the therapy of highly malignant TNBC.

Several methods for analyzing CgA using either monoclonal or polyclonal antibodies have been developed, which differ in their diagnostic performance. The present paper describes the results of a prospective multicenter study aimed at comparing the clinical value of the two most widely used commercially available CgA assay kits in patients affected by neuroendocrine tumors (NETs). Two hundred sixty-one patients from 40 different centers and 99 healthy subjects were evaluated. CgA levels were measured with two different methods, a two-step immunoradiometric assay (IRMA) and an enzyme-linked immunosorbent assay (ELISA). CgA was measured centrally by two reference laboratories, one of which used IRMA and the other ELISA, and it was measured by the participating institutions with the method routinely used by each of them. The major findings of the present study were: (i) the two assays for the determination of CgA present good diagnostic performance; (ii) both assays are robust and guarantee comparable results when applied in different settings (central vs local laboratory); (iii) the negative/positive cutoff points (87 ng/mL for IRMA and 21.3 U/L for ELISA) were established according to standardized criteria; (iv) the results obtained with the two assays in basal clinical samples of patients affected by NETs show an apparently satisfactory correlation (rs=0.843, p