High diagnostic accuracy of RT-QuIC assay in a prospective study of patients with suspected sCJD

The early and accurate in vivo diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD) is essential in order to differentiate CJD from treatable rapidly progressive dementias. Diagnostic investigations supportive of clinical CJD diagnosis include magnetic resonance imaging (MRI), electroencephalogram (EEG), 14-3-3 protein detection, and/or real-time quaking-induced conversion (RT-QuIC) assay positivity in the cerebrospinal fluid (CSF) or in other tissues. The total CSF tau protein concentration has also been used in a clinical setting for improving the CJD diagnostic sensitivity and specificity. We analyzed 182 CSF samples and 42 olfactory mucosa (OM) brushings from patients suspected of having sCJD with rapidly progressive dementia (RPD), in order to determine the diagnostic accuracy of 14-3-3, the total tau protein, and the RT-QuIC assay. A probable and definite sCJD diagnosis was assessed in 102 patients. The RT-QuIC assay on the CSF samples showed a 100% specificity and a 96% sensitivity, significantly higher compared with 14-3-3 (84% sensitivity and 46% specificity) and tau (85% sensitivity and 70% specificity); however, the combination of RT-QuIC testing of the CSF and OM samples resulted in 100% sensitivity and specificity, proving a significantly higher accuracy of RT-QuIC compared with the surrogate biomarkers in the diagnostic setting of patients with RPD. Moreover, we showed that CSF blood contamination or high protein levels might interfere with RT-QuIC seeding. In conclusion, we provided further evidence that the inclusion of an RT-QuIC assay of the CSF and OM in the diagnostic criteria for sCJD has radically changed the clinical approach towards the diagnosis

Expression of circulating miR-17-92 cluster and HDAC9 gene in atherosclerotic patients with unstable and stable carotid plaques

Aims: The miR-17-92 cluster and HDAC9 gene are involved in inflammatory, apoptotic, and angiogenic processes that are activated in the vulnerable carotid plaque. The aim of this research was to determine whether expression of one or more of the miRs of the cluster and/or HDAC9 expression could represent biomarkers for patients with unstable atherosclerotic carotid plaques. Materials and Methods: Plasma levels of miRs and HDAC9 expression in peripheral blood were analyzed by real-time PCR in patients with histologically classified stable or unstable plaques. Results: No differences were observed between the two groups. Discussion and Conclusions: Levels of the miR-17-92 cluster in plasma and HDAC9 gene expression in peripheral blood cannot be considered appropriate biomarkers to identify patients with unstable plaques at risk of rupture

In situ analysis of methylarginine

Aims: To (i) determine whether methylarginine-specific antibodies can be employed for standard immuno- histochemical analysis of paraffin-embedded tissues, (ii) analyse methylarginine expression in normal and neoplastic tissues and (iii) correlate methylarginine expression with that of protein arginine methyltrans- ferase (PRMT1), the predominant cellular arginine methyltransferase. Methods and results: Immunohistochemistry of normal and cancer tissues was performed utilizing three commercial polyclonal antibodies: anti-methylargi- nine-specific antibody (anti-mRG) raised against a methylarginine peptide, Control antibody (anti-RG), a control antiserum raised against a corresponding arginine peptide without any methylated residues and anti-PRMT1. Nuclear and ⁄ or cytoplasmic methylargi- nine expression was detected in all keratinized and non-keratinized epithelia. A preliminary survey of a series of thyroid, pancreatic, colonic and gastric can- cers identified a different pattern of methylarginine expression in comparison with normal tissue. A corre- lation between methylarginine staining and PRMT1 expression was found in all normal and cancer tissues analysed. Conclusion: Methylarginine-specific antibodies are capable of recognizing methylarginine proteins (MeRP) in paraffin-embedded tissues. Methylarginine proteins are expressed widely and show differences in subcellular localization in various organs and neo- plastic conditions. The efficient detection of methyl- proteins by standard immunohistochemistry provides a new tool to investigate the role of methylarginine proteins (MeRP) in biological processes including carcinogenesis

Tumors characterized by the presence of HMB45-positive perivascular epithelioid cell (PEC) - A novel entity in surgical pathology

Perivascular Epithelioid Cell (PEC) is a recently identified novel cell type expressing both markers of muscle nature and melanogenesis. PEC has been identified in numerous lesions, such as angiomyolipoma, lymphangioleiomyomatosis, lymphangioleiomyoma and clear cell 'sugar' tumor. We have proposed the unifying concept of a family of lesions characterised by the presence of PECs. Most of these lesions are strictly related to the genetic syndrome of tuberous sclerosis (TS). Some of these lesions can mimic other tumors, particularly clear cell carcinomas and clear cell sarcomas. The importance of a correct diagnosis is stressed by the fact that most PEC lesions have a benign clinical behaviour. Here we summarise our recent experience on this family of tumors

Extrahepatic Distal Cholangiocarcinoma vs. Pancreatic Ductal Adenocarcinoma: Histology and Molecular Profiling for Differential Diagnosis and Treatment

: Pancreatic ductal adenocarcinoma (PDAC) and distal cholangiocarcinoma (dCCA) are very aggressive tumors with a high mortality rate. Pancreas and distal bile ducts share a common embryonic development. Hence, PDAC and dCCA exhibit similar histological features that make a differential diagnosis during routine diagnostic practice challenging. However, there are also significant differences, with potential clinical implications. Even if PDAC and dCCA are generally associated with poor survival, patients with dCCA seem to present a better prognosis. Moreover, although precision oncology-based approaches are still limited in both entities, their most important targets are different and include alterations affecting BRCA1/2 and related genes in PDAC, as well as HER2 amplification in dCCA. Along this line, microsatellite instability represents a potential contact point in terms of tailored treatments, but its prevalence is very low in both tumor types. This review aims at defining the most important similarities and differences in terms of clinicopathological and molecular features between these two entities, also discussing the main theranostic implications derived from this challenging differential diagnosis