RESUMEN
BACKGROUND: Microsatellite instability (MSI) occurs in several cancer types and is commonly used for prognosis and as a predictive biomarker for immune checkpoint therapy. METHODS: We analyzed n = 263 formalin-fixed paraffin-embedded (FFPE) tumor specimens (127 colorectal cancer (CRC), 55 endometrial cancer (EC), 33 stomach adenocarcinoma (STAD), and 48 solid tumor specimens of other tumor types) with a capillary electrophoresis based multiplex monomorphic marker MSI-PCR panel and an amplicon-based NGS assay for microsatellite instability (MSI+). In total, n = 103 (39.2%) cases with a known defect of the DNA mismatch repair system (dMMR), determined by a loss in protein expression of MSH2/MSH6 (n = 48, 46.6%) or MLH1/PMS2 (n = 55, 53.4%), were selected. Cases with an isolated loss of MSH6 or PMS2 were excluded. RESULTS: The overall sensitivity and specificity of the NGS assay in comparison with the MSI-PCR were 92.2% and 98.8%. With CRC cases a nearly optimal concordance was reached (sensitivity 98.1% and specificity 100.0%). Whereas EC cases only show a sensitivity of 88.6% and a specificity of 95.2%, caused by several cases with instability in less than five monomorphic markers, which could be difficult to analyze by NGS (subtle MSI+ phenotype). CONCLUSIONS: MSI analysis of FFPE DNA by NGS is feasible and the results show a high concordance in comparison with the monomorphic marker MSI-PCR. However, cases with a subtle MSI+ phenotype, most frequently manifest in EC, have a risk of a false-negative result by NGS and should be preferentially analyzed by capillary electrophoresis.
Asunto(s)
Adenocarcinoma , Neoplasias Colorrectales , Neoplasias Endometriales , Femenino , Humanos , Inestabilidad de Microsatélites , Endonucleasa PMS2 de Reparación del Emparejamiento Incorrecto/metabolismo , Neoplasias Endometriales/diagnóstico , Neoplasias Endometriales/genética , Neoplasias Endometriales/patología , Adenocarcinoma/genética , Reacción en Cadena de la Polimerasa , Reparación de la Incompatibilidad de ADN/genética , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Repeticiones de Microsatélite , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismoRESUMEN
Objective. To perform a bibliometric analysis of pharmacy practice department chairs at US schools and colleges of pharmacy to determine factors associated with their level of scholarly productivity.Methods. Scopus was searched for all publications by pharmacy practice chairs from all pharmacy schools through August 11, 2020. Publication metrics (total number of publications and citations and the Hirsch-index (h-index), and year of first publication), as well as characteristics of the individual chair and institution were collected. Characteristics were compared across groups. A generalized linear model was used to determine the correlation between the total number of publications and h-index to school ranking by US News & World Report (USNWR).Results. One hundred forty-one pharmacy practice chairs were identified. The majority were male and at the rank of professor, with a similar proportion from public and private institutions. The median total number of publications and citations was 19 and 247, respectively, with a median h-index of eight. Compared with female chairs, male chairs had a higher median total of publications and citations and a higher h-index. Chairs at public institutions had a higher median total of publications and citations and a higher publication rate, h-index, and m quotient. The USNWR ranking for the school was significantly correlated with total publications and the h-index.Conclusion. Pharmacy practice chairs vary significantly in their scholarship productivity, although those at institutions with a larger emphasis on research were more prolific. Observed differences in the publication metrics of male and female chairs warrants further study to determine possible explanations for this finding and its potential impact.
