Differential expression profiles of cell-to-matrix-related molecules in adrenal cortical tumors: Diagnostic and prognostic implications

The molecular mechanisms of adrenocortical carcinoma development are incompletely defined. De-regulation of cellular-to-extracellular matrix interactions and angiogenesis appear among mechanisms associated to the malignant phenotype. Our aim was to investigate, employing PCR-based array profiling, 157 molecules involved in cell-to-matrix interactions and angiogenesis in a frozen series of 6 benign and 6 malignant adrenocortical neoplasms, to identify novel pathogenetic markers. In 14 genes, a significant dysregulation was detected in adrenocortical carcinomas as compared to adenomas, most of them being downregulated. Three exceptions—hyaluronan synthase 1 (HAS-1), laminin α3 and osteopontin genes—demonstrated an increased expression in adrenocortical carcinomas of 4.46, 4.23 and 20.32-fold, respectively, and were validated by immunohistochemistry on a series of paraffin-embedded tissues, including 20 adenomas and 73 carcinomas. Osteopontin protein, absent in all adenomas, was expressed in a carcinoma subset (25/73) (p = 0.0022). Laminin α3 and HAS-1 were mostly expressed in smooth muscle and endothelial cells of the vascular network of both benign and malignant adrenocortical tumors. HAS-1 was also detected in tumor cells, with a more intense pattern in carcinomas. In this group, strong expression was significantly associated with more favorable clinicopathological features. These data demonstrate that cell-to-matrix interactions are specifically altered in adrenocortical carcinoma and identify osteopontin and HAS-1 as novel potential diagnostic and prognostic biomarkers, respectively, in adrenal cortical tumors

BRCA1- A ssociated protein 1 (BAP1) immunohistochemical expression as a diagnostic tool in malignant pleural mesothelioma classification: A large retrospective study

Malignant pleural mesothelioma (MPM) is a highly aggressive disease with limited therapeutic options. Histological subtype remains among the most reliable prognostic factors, because the epithelioid subtype associated with the best prognosis and the sarcomatoid subtype with the worst. The biphasic subtype has an intermediate prognosis, but its definitive histological diagnosis may be challenging owing to the difficulty of assessing the neoplastic nature of the stromal component. Recent data identified BRCA1-associated protein 1 gene (BAP1) as one of the most frequently mutated genes in MPM. Immunohistochemical testing for BRCA1-associated protein 1 (BAP1) has been proposed to be predictive for the detection of BAP1 mutation in neoplastic cells. The aim of the present study was to define the diagnostic usefulness of immunohistochemical determination of BAP1 in MPM, with clinicopathological correlation

Nordic Walking promoted weight loss in overweight and obese people: A systematic review for future exercise prescription

The aim of this systematic review was to analyze the effect of Nordic Walking (NW) on anthropometric parameters, body composition, cardiovascular parameters, aerobic capacity, blood sample, and glucose tolerance in overweight and obese subjects. The main keywords "Nordic Walking" or "Pole Walking", associated with either "obese", "obesity", "overweight", or "weight loss" were used on the online database MEDLINE, PubMed, SPORTDiscus and Scopus. Additionally, references of the studies included were screened to identify eligible articles. Applying the inclusion and exclusion criteria, ten manuscripts were considered as eligible for this review. The results of the studies were categorized in several domains with regard to "anthropometric parameters and body composition", "cardiovascular parameters and aerobic capacity", and "blood sample and glucose tolerance". The results showed positive effects on the anthropometric parameters, body composition, cardiovascular parameters, blood sample, and glucose tolerance. The greatest improvements were observed in supervised and high weekly frequency of NW interventions. NW could be considered as an effective modality through which to involve the obese in physical activity. For weight loss, NW should be prescribed 4-5 times per week, at least 60 min per session, preferably combined with diet control

Adrenocortical tumors with myxoid features: a distinct morphologic and phenotypical variant exhibiting malignant behavior.

Myxoid changes have been rarely reported both in adrenocortical adenomas and carcinomas. The recent observation by our group of an adrenal myxoid tumor with morphologically borderline features, but aggressive clinical behavior prompted us to review a series of 196 adrenocortical lesions, comprising 122 carcinomas and 74 adenomas, to define the morphologic, phenotypical and clinical characteristics of adrenocortical tumors with myxoid features. Fourteen cases, including 12 carcinomas and 2 borderline tumors, formed the basis of this report, and were characterized by a variably abundant myxoid component (from 5% to 90% of tumor) and 2 distinct cellular growth patterns: the first (10 cases), mostly associated with a predominant myxoid stromal component, was made of small cells with mild atypia arranged in cords and microcysts; the second (4 cases) was characterized by focal myxoid changes in tumors otherwise similar to conventional adrenocortical carcinoma, with large atypical cells having an eosinophilic cytoplasm and a diffuse or nodular architecture. The above mentioned patterns were absent in all adenomas reviewed. A peculiar reactivity to neurofilaments was seen, mostly associated to the presence of predominant rather that focal myxoid stromal changes, and in 40% of conventional adrenocortical carcinomas, thus representing an undescribed potential pitfall in the differential diagnosis of adrenal lesions. Myxoid adrenocortical tumors probably represent a rare but histologically and phenotipically distinct entity and, although rare cases of benign lesions are on record, they seem to be generally associated to morphologic and clinical features of malignancy

Comparative diagnostic and prognostic performances of the hematoxylin-eosin and phospho-histone H3 mitotic count and Ki-67 index in adrenocortical carcinoma

Mitotic count on hematoxylin and eosin slides is a fundamental morphological criterion in the diagnosis and grading of adrenocortical carcinoma in any scoring system employed. Moreover, it is the unique term strongly associated with patient's prognosis. Phospho-histone H3 is a mitosis-specific antibody, which was already proven to facilitate mitotic count in melanoma and other tumors. Therefore, a study was designed to assess the diagnostic and prognostic role of phospho-histone H3 in 52 adrenocortical carcinomas, comparing manual and computerized count to standard manual hematoxylin- and eosin-based method and Ki-67 index. Manual hematoxylin and eosin and phospho-histone H3 mitotic counts were highly correlated (r=0.9077, P50%) Ki-67 values. We conclude that (a) phospho-histone H3 staining is a useful diagnostic complementary tool to standard hematoxylin and eosin mitotic count, enabling optimal mitotic figure evaluation (including atypical mitotic figures) even in adrenocortical carcinomas with a low mitotic index and with a very high reproducibility; (b) Ki-67 proved to be the best prognostic indicator of overall survival, being superior to the mitotic index, irrespective of the method (standard on hematoxylin and eosin or phospho-histone H3-based) used to count mitotic figures

The Effect of Exercise Training on Irisin Secretion in Patients with Type 2 Diabetes: A Systematic Review

Introduction: Irisin is a myokine considered to be a potential mediator of exercise-induced energy metabolism and its secretion is known to promote the browning of beige fat cells in white adipose tissue. However, it is currently not known which exercise protocol is the best to enhance irisin concentration in patients with type 2 diabetes (T2D). Objective: The purpose of this study is to provide a review investigating the irisin response to different exercise training modalities and intensities in T2D. Methods: A systematic literature search was performed in May 2022. Results: After the selection process from 938 articles, six studies were included. Selected papers presented different exercise training interventions regarding intensity and modality. One study reported no significant differences in serum irisin levels after exercise training, whereas the other five showed a higher increase in serum irisin levels after exercise training with higher differences in irisin secretion after high-intensity training (HIT). No consideration was possible on exercise modalities. Conclusions: The impact of training intensity and modality was found to be partly discordant but data seem to suggest that HIT promotes greater irisin secretion. Despite the limited evidence, HIT, both in interval and continuous modalities, could be suggested as valid exercise training to increase circulating irisin in patients with T2D