Programmed death ligand-1 (PD-L1) expression as determined by immunohistochemistry (IHC) is potentially predictive of clinical outcome. The aim of this study was to assess the concordance of reported ...PD-L1 IHC assays and investigate factors influencing variability. Consecutive sections from 20 non-small cell lung cancers (NSCLCs) comprising resection, core biopsy, cytology and pleural fluid samples underwent IHC with 5 different antibody/autostainer combinations: 22C3/Link48, 28-8/BOND-MAX, E1L3N/BOND-MAX, SP142/BenchMark and SP263/BenchMark. PD-L1 RNA levels were assessed using RNAscope. The frequency of positive cases using scoring thresholds from clinical trials was 72%, 33%, 61%, 56%, and 33% for the 5 IHC protocols respectively, and 33% for RNAscope. Pairwise agreement on the classification of cases as positive or negative for PD-L1 expression ranged from 61%-94%. On a continuous scale, the lowest correlation was between 28-8/BOND-MAX and SP142/BenchMark (R
=0.25) and highest was between 22C3/Link48 and E1L3N/BOND-MAX (R
=0.71). When cases were ordered according to tumor cell (TC)%, a similar ranking of cases across IHC protocols could be observed, albeit with different quanta and limits of detection. Single-slide OPAL 7-color fluorescence IHC analysis revealed a high degree of co-localization of staining from the 5 PD-L1 antibodies. Using SP142 antibody in a BOND-MAX protocol led to increased TC% quanta, while retaining a similar ranking of samples according to TC%. The results of this study highlight tumor PD-L1 status can vary significantly according to IHC protocol. Protocol-dependent staining intensities and nominated thresholds for positivity contribute to this variability, while the antibody used appears to be less of a factor.
Objetivos: determinar la utilidad de las características morfológicas, fenotípicas y citogenéticas frente a un algoritmo diagnóstico validado para diferenciar entre una NPB, LPB o MPB. Materiales y ...métodos: revisamos cinco casos multicéntricos, retrospectivos con diagnósticos previos de MPB (n=3) y LPB (n=2); los datos clínicos y paraclínicos fueron anotados. Se valoró la consistencia del diagnóstico inicial usando el algoritmo de Mori mediante el status del EBER, Ki67 y signos modificados de mieloma (Proteína M, lesiones líticas y relación kappa/lambda >100), para orientar un LPB, MPB o NPB. Dicha orientación se comparó con la morfología, inmunofenotipo, citogenética y estudios moleculares disponibles para tratar de resolver el interrogante si solo el algoritmo es suficiente.
We report the results of pathologic examinations of 2 fetuses from women in Colombia with Zika virus infection during pregnancy that revealed severe central nervous system defects and potential ...associated abnormalities of the eye, spleen, and placenta. Amniotic fluid and tissues from multiple fetal organs tested positive for Zika virus.
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DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Heterozygous germline TP53 gene mutations result in Li-Fraumeni Syndrome (LFS). Breast cancer (BC) is the most frequent tumor in young women with LFS. An important issue related to BC in the Mexican ...population is the average age at diagnosis, which is approximately 11 years younger than that of patients in the United States (U.S.) and Europe. The aim of this study was to determine the prevalence of germline mutations in TP53 among young Mexican BC patients.
We searched for germline mutations in the TP53 gene using targeted next-generation sequencing (NGS) in 78 BC patients younger than 45 years old (yo) who tested negative for BRCA1/2 mutations. A group of 509 Mexican women aged 45yo or older without personal or family BC history (parents/grandparents) was used as a control.
We identified five patients with pathogenic variants in the TP53 gene, equivalent to 6.4% (5/78). Among patients diagnosed at age 36 or younger, 9.4% (5/55) had pathogenic TP53 mutations. Three of these variants were missense mutations (c.844C > T, c.517G > A, and c.604C > T), and the other two mutations were frameshifts (c.291delC and c.273dupC) and had not been reported previously. We also identified a variant of uncertain clinical significance (VUS), c.672G > A, which causes a putative splice donor site mutation. All patients with TP53 mutations had high-grade and HER2-positive tumors. None of the 509 patients in the healthy control group had mutations in TP53.
Among Mexican BC patients diagnosed at a young age, we identified a high proportion with germline mutations in the TP53 gene. All patients with the TP53 mutations had a family history suggestive of LFS. To establish the clinical significance of the VUS found, additional studies are needed. Pathogenic variants of TP53 may explain a substantial fraction of BC in young women in the Mexican population. Importantly, none of these mutations or other pathological variants in TP53 were found in the healthy control group.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In breast cancer (BC), the presence of cancer stem cells (CSCs) has been related to relapse, metastasis, and radioresistance. Radiotherapy (RT) is an extended BC treatment, but is not always ...effective. CSCs have several mechanisms of radioresistance in place, and some miRNAs are involved in the cellular response to ionizing radiation (IR). Here, we studied how IR affects the expression of miRNAs related to stemness in different molecular BC subtypes. Exposition of BC cells to radiation doses of 2, 4, or 6 Gy affected their phenotype, functional characteristics, pluripotency gene expression, and in vivo tumorigenic capacity. This held true for various molecular subtypes of BC cells (classified by ER, PR and HER‐2 status), and for BC cells either plated in monolayer, or being in suspension as mammospheres. However, the effect of IR on the expression of eight stemness‐ and radioresistance‐related miRNAs (miR‐210, miR‐10b, miR‐182, miR‐142, miR‐221, miR‐21, miR‐93, miR‐15b) varied, depending on cell line subpopulation and clinicopathological features of BC patients. Therefore, clinicopathological features and, potentially also, chemotherapy regimen should be both taken into consideration, for determining a potential miRNA signature by liquid biopsy in BC patients treated with RT. Personalized and precision RT dosage regimes could improve the prognosis, treatment, and survival of BC patients.
Breast cancer stem cells (BCSCs) have been related to relapse, metastasis, self‐renewal, and radioresistance. Ionizing radiation (IR) modifies miRNA expression. miRNAs related with BCSCs, tumorigenic process, radioresistance and poor prognosis showed variability in the expression according to IR dose, BC molecular subtypes and clinicopathological features. This miRNA signature could improve prognosis, treatments, and survival of BC patients by using precision radiotherapy dosage regimes.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Phenol is a recalcitrant anthropogenic compound whose presence has been reported in both wastewater and drinking water; human exposure to phenolic substances can lead to health problems. The ...degradation of phenol (measured as COD decrease) through solar heterogeneous photocatalysis with immobilized TiO2 was performed in two different reactors: a flat-plate reactor (FPR) and a compound parabolic collector (CPC). A 23 full factorial experimental design was followed. The variables were the presence of TiO2, H2O2 addition, and the type of reactor. Data were fitted to the pseudo-first-order reaction-rate-kinetics model. The rate constant for photocatalytic phenol degradation with 1 mM of H2O2 was 6.6 × 10−3 min−1 for the FPR and 5.9 × 10−3 min−1 in the CPC. The calculated figures of merit were analyzed with a MANCOVA, with UV fluence as a covariate. An ANCOVA showed that the type of reactor, H2O2 addition, or fluence had no statistically significant effect on the results, but there was for the presence of TiO2. According to the MANCOVA, fluence and TiO2 presence were significant (p < 0.05). The CPC was on average 17.4% more efficient than the FPR when it came to collector area per order (ACO) by heterogeneous photocatalysis and 1 mM H2O2 addition.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Access to drinking water is a human right recognized by the United Nations. It is estimated that more than 2.1 billion people lack access to drinking water with an adequate microbiological quality, ...which is associated to 80% of all diseases, as well as with millions of deaths caused by infections, especially in children. Water disinfection technologies need a continuous improvement approach to meet the growing demand caused by population growth and climate change. Heterogeneous photocatalysis with semiconductors, which is an advanced oxidation process, has been proposed as a sustainable technology for water disinfection, as it does not need addition of any chemical substance and it can make use of solar light. Nevertheless, the technology has not been deployed industrially and commercially yet, mainly because of the lack of efficient reactor designs to treat large volumes of water, as most research focus on lab-scale experimentation. Additionally, very few applications are often tested employing actual sunlight. The present work provide a perspective on the operation trends and advances of solar heterogeneous photocatalytic reactors for water disinfection by systematically analyzing pertaining literature that made actual use of sunlight, with only 60 reports found out of the initially 1044 papers detected. These reports were discussed in terms of reactor employed, photocatalyst used, microorganism type, overall disinfection efficiency, and location. General prospects for the progression of the technology are provided as well.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Arsenic (As) poses a threat to human health. In 2014, more than 200 million people faced arsenic exposure through drinking water, as estimated by the World Health Organization. Additionally, it is ...estimated that drinking water with proper microbiological quality is unavailable for more than 1 billion people. The present work analyzed a solar heterogeneous photocatalytic (HP) process for arsenite (AsIII) oxidation and coliform disinfection from a real groundwater matrix employing two reactors, a flat plate reactor (FPR) and a compound parabolic collector (CPC), with and without added hydrogen peroxide (H2O2). The pseudo first-order reaction model fitted well to the As oxidation data. The treatments FPR–HP + H2O2 and CPC–HP + H2O2 yielded the best oxidation rates, which were over 90%. These treatments also exhibited the highest reaction rate constants, 6.7 × 10−3 min−1 and 6.8 × 10−3 min−1, respectively. The arsenic removal rates via chemical precipitation reached 98.6% and 98.7% for these treatments. Additionally, no coliforms were detected at the end of the process. The collector area per order (ACO) for HP treatments was on average 75% more efficient than photooxidation (PO) treatments. The effects of the process independent variables, H2O2 addition, and light irradiation were statistically significant for the AsIII oxidation reaction rate (p < 0.05).
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