Challenges and limitation of MTAP immunohistochemistry in diagnosing desmoplastic mesothelioma/sarcomatoid pleural mesothelioma with desmoplastic features

AimGenomic-based ancillary assays including immunohistochemistry (IHC) for BRCA-1 associated protein-1 (BAP1) and methylthioadenosine phosphorylase (MTAP), and fluorescence in situ hybridization (FISH) for CDKN2A are effective for differentiating pleural mesothelioma (PM) from reactive mesothelial proliferations. We previously reported a combination of MTAP and BAP1 IHC effectively distinguishes sarcomatoid PM from fibrous pleuritis (FP). Nevertheless, cases of sarcomatoid PM with desmoplastic features (desmoPM) are encountered where the IHC assessment is unclear.Methods and resultsWe evaluated assessment of MTAP IHC, BAP1 IHC, and CDKN2A FISH in 20 desmoPM compared to 24 FP. MTAP and BAP1 IHC could not be assessed in 11 (55 %) and 10 (50 %) cases, respectively, due to loss or faint immunoreactivity of internal positive control cells, while CDKN2A FISH could be evaluated in all cases. The sensitivities for MTAP loss, BAP1 loss, and CDKN2A homozygous deletion in desmoPM were 40 %, 10 %, and 100 %. A combination of MTAP loss and BAP1 loss yielded 45 % of sensitivity.ConclusionsMTAP IHC is a useful surrogate diagnostic marker in differentiating ordinary sarcomatoid PM from FP, but its effectiveness is limited in desmoPM. CDKN2A FISH is the most effective diagnostic assays with 100 % sensitivity and specificity in discriminating desmoPM from FP in the facilities where the FISH assay is available.     

Alanine transaminase is predominantly increased in the active phase of anti-HMGCR myopathy

Autoantibodies against 3?hydroxy-3-methylglutaryl-CoA reductase (HMGCR) and the signal recognition particle (SRP) are representative antibodies causing immune-mediated necrotizing myopathies (IMNM), called as anti-HMGCR and anti-SRP myopathies, respectively. Here, we analyzed the differences in routine blood test results between 56 anti-HMGCR and 77 anti-SRP myopathy patients. A higher alanine transaminase (ALT) level and a lower aspartate transaminase (AST)/ALT ratio were observed in anti-HMGCR myopathy patients [ALT, 265.7 ± 213.3 U/L (mean ± standard deviation); AST/ALT ratio, 0.88 ± 0.32] than in anti-SRP-myopathy patients (ALT, 179.3 ± 111.2 U/L, p < 0.05; AST/ALT ratio, 1.28 ± 0.40, p < 0.01). In the active phase, anti-HMGCR myopathy often showed ALT predominance, whereas anti-SRP myopathy often showed AST predominance. In addition, there were differences in erythrocyte sedimentation rate (ESR), total cholesterol (TChol) level, and high-density lipoprotein (HDL) level between anti-HMGCR and anti-SRP myopathies (ESR: HMGCR, 24.4 ± 20.8 mm/1 h; SRP, 35.7 ± 26.7 mm/1 h, p = 0.0334; TChol: HMGCR, 226.7 ± 36.6 mg/dL; SRP, 207.6 ± 40.8 mg/dL, p = 0.0163; HDL: HMGCR, 58.4 ± 13.9 mg/dL; SRP, 46.2 ± 17.3 mg/dL, p < 0.01). Additional studies on the differences in routine blood test results may further reveal the pathomechanisms of IMNM.     

Review of Variables Associated With Positive Surgical Margins Using Scout Reflector Localizations for Breast Conservation Therapy

ObjectiveTo evaluate factors contributing to positive surgical margins associated with reflector guidance for patients undergoing breast conserving therapy for malignancy.Materials and MethodsA retrospective IRB-approved review of our institutional database was performed for malignant breast lesions preoperatively localized from January 1, 2018 to December 31, 2020. The following data was recorded using electronic medical records: lesion type and grade, lesion location, reflector and wire placement modality, use of intraoperative ultrasound, margin status, patient age, family history, BMI, and final pathology. Statistical analysis was performed with univariate summary statistics and logistic regression. P < .05 was significant.ResultsA total of 606 image-guided pre-surgical localizations were performed for lumpectomies of breast malignancies. A total of 352 of 606 (58%) wire localizations and 254 of 606 (42%) SCOUT reflector localizations were performed. Sixty out of 352 (17%) of wire-localized patients had positive surgical margins, whereas forty-eight out of 254 (19%) of reflector-localized patients had positive surgical margins. (OR = 1.12, P value: .59). For reflector guided cases, the use of intraoperative ultrasound (IOUS) was associated with decreased positive margin status (OR = 0 .28, 95% CI = [0.14, 0.58]) while in situ disease was associated with increased positive margin status (OR = 1.99, 95% CI = [1.05, 3.75]). No association between modality used for localization (mammography vs. ultrasound) and positive margin status was observed (OR = 0.63, 95% CI = [0.33, 1.19]). No association between positive margins and age, family history, tumor location and BMI was observed.ConclusionFor reflector guided surgeries, the use of IOUS was associated with decreased positive margins, by contrast the presence of ductal carcinoma in situ was associated with increased positive margins. There was no statistically significant difference in surgical outcomes for reflector-guided localization compared to wire localizations of the breast.     

The proteome microenvironment determines the protective effect of preconditioning in cisplatin-induced acute kidney injury

1. Download high-res image (341KB)
2. Download full-size image

     

Development and validation of the EUROFORGEN NAME (North African and Middle Eastern) ancestry panel

Inference of biogeographic origin is an important factor in clinical, population and forensic genetics. The information provided by AIMs (Ancestry Informative Markers) can allow the differentiation of major continental population groups, and several AIM panels have been developed for this purpose. However, from these major population groups, Eurasia covers a wide area between two continents that is difficult to differentiate genetically. These populations display a gradual genetic cline from West Europe to South Asia in terms of allele frequency distribution. Although differences have been reported between Europe and South Asia, Middle East populations continue to be a target of further investigations due to the lack of genetic variability, therefore hampering their genetic differentiation from neighboring populations. In the present study, a custom-built ancestry panel was developed to analyze North African and Middle Eastern populations, designated the ‘NAME’ panel. The NAME panel contains 111 SNPs that have patterns of allele frequency differentiation that can distinguish individuals originating in North Africa and the Middle East when combined with a previous set of 126 Global AIM-SNPs.     

Deep learning with biopsy whole slide images for pretreatment prediction of pathological complete response to neoadjuvant chemotherapy in breast cancer：A multicenter study

IntroductionPredicting pathological complete response (pCR) for patients receiving neoadjuvant chemotherapy (NAC) is crucial in establishing individualized treatment. Whole-slide images (WSIs) of tumor tissues reflect the histopathologic information of the tumor, which is important for therapeutic response effectiveness. In this study, we aimed to investigate whether predictive information for pCR could be detected from WSIs.Materials and methodsWe retrospectively collected data from four cohorts of 874 patients diagnosed with biopsy-proven breast cancer. A deep learning pathological model (DLPM) was constructed to predict pCR using biopsy WSIs in the primary cohort, and it was then validated in three external cohorts. The DLPM could generate a deep learning pathological score (DLPs) for each patient; stromal tumor-infiltrating lymphocytes (TILs) were selected for comparison with DLPs.ResultsThe WSI feature-based DLPM showed good predictive performance with the highest area under the curve (AUC) of 0.72 among the cohorts. Alternatively, the combination of the DLPM and clinical characteristics offered a better prediction performance (AUC >0.70) in all cohorts. We also evaluated the performance of DLPM in three different breast subtypes with the best prediction for the triple-negative breast cancer (TNBC) subtype (AUC: 0.73). Moreover, DLPM combined with clinical characteristics and stromal TILs achieved the highest AUC in the primary cohort (AUC: 0.82) and validation cohort 1 (AUC: 0.80).ConclusionOur study suggested that WSIs integrated with deep learning could potentially predict pCR to NAC in breast cancer. The predictive performance will be improved by combining clinical characteristics. DLPs from DLPM can provide more information compared to stromal TILs for pCR prediction.     

Quality of oral anticoagulation control in Chinese patients with non-valvular atrial fibrillation: a prospective controlled study

Abstract

Objective

The sex, age, medical history, treatment, tobacco use, race risk (SAMe-TT₂R₂) Score; the sex, age, medical history, treatment, tobacco use, genotype combination (SAMe-TT₂G₂) Score; and the so-called modified SAMe-TT₂R₂ scores have been proposed to predict the anticoagulation quality for patients with non-valvular atrial fibrillation (NVAF). The data from a prospective controlled study is used to validate the SAMe-TT₂R₂ and SAMe-TT₂G₂ scores in Chinese NVAF patients treated with warfarin and to evaluate the association of factors with time in therapeutic range (TTR) to predict the quality of oral anticoagulation control.     

The emergence of human Powassan virus infection in North America

Powassan virus (POWV) is a tickborne flavivirus discovered in Ontario, Canada in 1958 that causes long-term neurological sequelae in about half the reported cases and death in a little more than 10 % of cases. The incidence of POWV disease is rising in the United States but there is limited understanding of the scope and causes of recent changes in POWV epidemiology. We focus on quantifying the increase in human POWV disease incidence and infection prevalence in the United States. We also examine differences in the frequency of symptomatic cases and asymptomatic or mildly symptomatic cases, as well as limitations in national and state surveillance for POWV infection. We searched SCOPUS for all articles containing original POWV prevalence research, case studies, or literature reviews published in English. Case studies were supplemented by Morbidity and Mortality Weekly Report POWV data from the Centers for Disease Control and Prevention (CDC) and surveillance information from state health department websites. An increase in the number of POWV cases has been reported in the United States over the past 50 yr, and the geographic range of human POWV cases has expanded. The age distribution of symptomatic POWV cases has shifted, with significantly more individuals over 40 yr old being diagnosed after 1998. The emergence of POWV is due in large part to: (i) a change in transmission of POWV from a vector that rarely bites people (Ixodes cookei) to a new vector that often bites people (Ixodes scapularis) and has expanded its geographic range, (ii) enhanced surveillance efforts for arboviruses, and (iii) a greater awareness of POWV infection.