The cross-section measurement of Antimony (Sb) is pivotal to modify or stagnate the rate of neutron flux in nuclear reactors. Neutron induced reaction cross-section data for isotopes of Sb is meagre as per reported in EXFOR. A comprehensive attempt has been made to analyse the reaction cross-section of 121Sb and 123Sb at monoenergetic neutron energy of 14.96 ± 0.03 MeV. The experiment was performed at the Neutron and Ion Irradiation Facility, Institute for Plasma Research (IPR), Gujarat (India). The 27Al(n,α)24Na reaction is used to monitor the flux and to estimate the cross-section of (n,2n), (n,p) reactions using neutron activation technique. Monoenergetic neutrons generated by D-T fusion reaction were bombarded on the natural sample of Sb to induce radioactivity. A High Purity Germanium detector (HPGe) with a resolution of 2.1 keV at 1.33 MeV γ-ray energy of 60Co based on GENIE software was used for the counting of emitted gamma photo peaks. Calculated results are compared with the existing studies from EXFOR. The cross-section values are estimated using TALYS-2.0 statistical code by employing different input parameters, along with the latest Evaluated Nuclear data libraries (ENDF/B-VIII.0, JEFF-3.3). To obtain more precise data, uncertainties from various parameters are propagated using the correlation coefficients among all the parameters. This systematic detailed covariance analysis helps to reduce the present discrepancies and to refine the nuclear data.
- Klíčová slova
- Antimony, Covariance analysis, Cross-section, EXFOR, HPGe detector, TALYS-2.0,
- Publikační typ
- časopisecké články MeSH
Pathogenic mutations in the genes associated with tuberous sclerosis complex (TSC)/mTOR pathway are linked to histologically diverse renal cell neoplasms, including eosinophilic solid and cystic renal cell carcinoma (ESC RCC), low grade oncocytic tumor (LOT), eosinophilic vacuolated tumor (EVT), and xanthomatous giant cell renal cell carcinoma (XGC RCC). Here, we validate a TSC2 immunohistochemistry (IHC) assay by comparison to genomic data in these neoplasms. Automated TSC2 IHC was performed on formalin-fixed paraffin embedded (FFPE) tissues from 38 genetically-confirmed TSC/mTOR-associated renal tumors (6 ESCs, 16 EVTs, 13 LOTs, 2 XGC and 1 clear cell RCC) and visually scored in a semi-dichotomous fashion compared to internal control tissue. The positive predictive value (PPV) of TSC2 protein loss for underlying pathogenic mutation in TSC2 was 92% (11/12), while the negative predictive value (NPV) of intact TSC2 by IHC for lack of underlying pathogenic mutation in TSC2 was 81% (21/26). Intact TSC2 by IHC was 95% (21/22) specific for absence of underlying pathogenic TSC2 mutation. All the cases lacking TSC2 mutation with intact TSC2 protein had an underlying mutation in TSC1, MTOR or PIK3CA. Loss of TSC2 was 77% (10/13) sensitive for underlying TSC2 truncation mutations and 33% (1/3) sensitive for underlying TSC2 missense mutations. Overall, 73% (8/11) tumors with TSC2 IHC loss and underlying pathogenic alterations in TSC2 showed heterogeneous protein loss, with rare interspersed positively staining tumor cells. These data support TSC2 IHC as a potentially useful assay for the diagnostic workup of renal tumors suspected to belong to the TSC/mTOR-associated subgroups.
- Klíčová slova
- Genetic validation, Immunohistochemistry, Renal cell carcinoma, TSC2,
- MeSH
- dospělí MeSH
- imunohistochemie * metody MeSH
- karcinom z renálních buněk * genetika patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mutace MeSH
- mutační analýza DNA MeSH
- nádorové biomarkery * genetika analýza MeSH
- nádorové supresorové proteiny * genetika analýza MeSH
- nádory ledvin * genetika patologie MeSH
- prediktivní hodnota testů MeSH
- reprodukovatelnost výsledků MeSH
- signální transdukce genetika MeSH
- TOR serin-threoninkinasy * genetika metabolismus analýza MeSH
- tuberin genetika MeSH
- tuberózní skleróza * genetika MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- validační studie MeSH
- Názvy látek
- MTOR protein, human MeSH Prohlížeč
- nádorové biomarkery * MeSH
- nádorové supresorové proteiny * MeSH
- TOR serin-threoninkinasy * MeSH
- TSC2 protein, human MeSH Prohlížeč
- tuberin MeSH
Oncocytic renal neoplasms are a major source of diagnostic challenge in genitourinary pathology; however, they are typically nonaggressive in general, raising the question of whether distinguishing different subtypes, including emerging entities, is necessary. Emerging entities recently described include eosinophilic solid and cystic renal cell carcinoma (ESC RCC), low-grade oncocytic tumor (LOT), eosinophilic vacuolated tumor (EVT), and papillary renal neoplasm with reverse polarity (PRNRP). A survey was shared among 65 urologic pathologists using SurveyMonkey.com (Survey Monkey, Santa Clara, CA, USA). De-identified and anonymized respondent data were analyzed. Sixty-three participants completed the survey and contributed to the study. Participants were from Asia (n = 21; 35%), North America (n = 31; 52%), Europe (n = 6; 10%), and Australia (n = 2; 3%). Half encounter oncocytic renal neoplasms that are difficult to classify monthly or more frequently. Most (70%) indicated that there is enough evidence to consider ESC RCC as a distinct entity now, whereas there was less certainty for LOT (27%), EVT (29%), and PRNRP (37%). However, when combining the responses for sufficient evidence currently and likely in the future, LOT and EVT yielded > 70% and > 60% for PRNRP. Most (60%) would not render an outright diagnosis of oncocytoma on needle core biopsy. There was a dichotomy in the routine use of immunohistochemistry (IHC) in the evaluation of oncocytoma (yes = 52%; no = 48%). The most utilized IHC markers included keratin 7 and 20, KIT, AMACR, PAX8, CA9, melan A, succinate dehydrogenase (SDH)B, and fumarate hydratase (FH). Genetic techniques used included TSC1/TSC2/MTOR (67%) or TFE3 (74%) genes and pathways; however, the majority reported using these very rarely. Only 40% have encountered low-grade oncocytic renal neoplasms that are deficient for FH. Increasing experience with the spectrum of oncocytic renal neoplasms will likely yield further insights into the most appropriate work-up, classification, and clinical management for these entities.
- Klíčová slova
- Emerging, Eosinophilic, Oncocytic, Renal neoplasms, Uropathologists,
- MeSH
- karcinom z renálních buněk * patologie diagnóza MeSH
- lidé MeSH
- nádorové biomarkery analýza MeSH
- nádory ledvin * patologie diagnóza MeSH
- oxyfilní adenom * patologie diagnóza MeSH
- patologové * MeSH
- průzkumy a dotazníky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- nádorové biomarkery MeSH
Low-grade oncocytic tumour (LOT) of the kidney has recently emerged as a potential novel tumour type. Despite similarity to oncocytoma or eosinophilic chromophobe renal cell carcinoma, it shows diffuse keratin 7 immunohistochemistry (IHC) and negative KIT (CD117), which differs from both. We aimed to identify the molecular characteristics of these tumours. Seventeen tumours (one male, 16 female, nine previously published) fitting the original description of this entity (solid eosinophilic cell morphology, often with areas of tumour cells loosely stretched in oedematous stroma, and the above IHC features) were analysed with a next-generation sequencing panel of 324 cancer-associated genes from formalin-fixed, paraffin-embedded tissue. All tumours harboured at least one alteration in either TSC1 (n = 7, 41%), TSC2 (n = 2, 12%), MTOR (n = 5, 29%) or PIK3CA (n = 4, 24%). Four tumours harboured a second alteration, including two NF2, one each in conjunction with MTOR and TSC2 alterations, one PTEN with TSC1 alteration and one tumour with both MTOR and TSC1 alterations. No other renal cancer-related or recurring gene alterations were identified. In addition to the previously described IHC findings, 16 of 16 were positive for GATA3. Eleven patients with follow-up had no metastases or recurrent tumours. Recurrent tuberous sclerosis/MTOR pathway gene alterations in LOT support its consideration as a distinct morphological, immunohistochemical and genetic entity. PIK3CA is another pathway member that may be altered in these tumours. Further study will be necessary to determine whether tumour behaviour or syndromic associations differ from those of oncocytoma and chromophobe carcinoma, warranting different clinical consideration.
- Klíčová slova
- PIK3CA, MTOR, TSC1, TSC2, low-grade oncocytic tumour, oncocytoma,
- MeSH
- fosfatidylinositol-3-kinasy třídy I genetika MeSH
- karcinom z renálních buněk * genetika MeSH
- ledviny MeSH
- lidé MeSH
- lokální recidiva nádoru MeSH
- mutace MeSH
- nádory ledvin * genetika MeSH
- oxyfilní adenom * genetika MeSH
- TOR serin-threoninkinasy genetika MeSH
- transkripční faktor GATA3 genetika MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- fosfatidylinositol-3-kinasy třídy I MeSH
- GATA3 protein, human MeSH Prohlížeč
- MTOR protein, human MeSH Prohlížeč
- PIK3CA protein, human MeSH Prohlížeč
- TOR serin-threoninkinasy MeSH
- transkripční faktor GATA3 MeSH
The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles ("MISEV") guidelines for the field in 2014. We now update these "MISEV2014" guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.
- Klíčová slova
- ectosomes, exosomes, extracellular vesicles, guidelines, microparticles, microvesicles, minimal information requirements, reproducibility, rigor, standardization,
- Publikační typ
- časopisecké články MeSH