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Integrating clinicopathological and molecular data to assess the biological behavior of uterine inflammatory myofibroblastic tumors
QH. Bui, M. Krausová, N. Hájková, J. Hojný, M. Kendall Bártů, R. Vránková, M. Kalousová, F. Frühauf, M. Michal, K. Němejcová, I. Stružinská, P. Dundr
Jazyk angličtina Země Německo
Typ dokumentu časopisecké články
- MeSH
- dospělí MeSH
- imunohistochemie MeSH
- inhibitor p16 cyklin-dependentní kinasy MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové biomarkery * genetika analýza MeSH
- nádory dělohy * patologie genetika MeSH
- nádory ze svalové tkáně * patologie genetika MeSH
- senioři MeSH
- vysoce účinné nukleotidové sekvenování MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Assessing the biological behavior of uterine inflammatory myofibroblastic tumors (IMTs) remains challenging. This study evaluated previously proposed risk schemes and features in 9 IMTs (6 indolent, 3 aggressive) by integrating clinicopathological features, immunohistochemistry, and next-generation sequencing (NGS). High-risk features (necrosis, infiltrative growth, nuclear atypia) were present in both groups, with LVSI in 1/3 of aggressive IMTs. Aberrant p16 expression and CDKN2A/2B deletions were noted in 2/3 aggressive cases. All cases harbored ALK fusions, wild-type p53, and lacked pathogenic gene mutations. Aggressive cases harbored arm-level and segmental copy number gains/losses at chr 1, 2, X, and had significantly reduced AR expression. The clinicopathological risk stratification score (CRSS) predicted the biological behavior correctly in cases with complete clinicopathological data (size, mitoses, age, infiltrative growth). Two morcellated cases (one indolent and one aggressive) would have been predicted as low risk based solely on the absence of pathogenic mutations. Hereby, the reliability of the proposed CRSS was confirmed. Aberrant p16 expression predicted malignant behavior in 2/3 aggressive cases. Absence of pathogenic mutations or presence of large scale CNVs does not seem to be a predictor of clinical behavior. Additional studies and NGS analyses of more cases may improve risk stratification for patients with incomplete clinicopathological information and may reveal additional risk stratifiers (such as the suggested large-scale CNVs or AR downregulation) for IMTs.
Citace poskytuje Crossref.org
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- $a Assessing the biological behavior of uterine inflammatory myofibroblastic tumors (IMTs) remains challenging. This study evaluated previously proposed risk schemes and features in 9 IMTs (6 indolent, 3 aggressive) by integrating clinicopathological features, immunohistochemistry, and next-generation sequencing (NGS). High-risk features (necrosis, infiltrative growth, nuclear atypia) were present in both groups, with LVSI in 1/3 of aggressive IMTs. Aberrant p16 expression and CDKN2A/2B deletions were noted in 2/3 aggressive cases. All cases harbored ALK fusions, wild-type p53, and lacked pathogenic gene mutations. Aggressive cases harbored arm-level and segmental copy number gains/losses at chr 1, 2, X, and had significantly reduced AR expression. The clinicopathological risk stratification score (CRSS) predicted the biological behavior correctly in cases with complete clinicopathological data (size, mitoses, age, infiltrative growth). Two morcellated cases (one indolent and one aggressive) would have been predicted as low risk based solely on the absence of pathogenic mutations. Hereby, the reliability of the proposed CRSS was confirmed. Aberrant p16 expression predicted malignant behavior in 2/3 aggressive cases. Absence of pathogenic mutations or presence of large scale CNVs does not seem to be a predictor of clinical behavior. Additional studies and NGS analyses of more cases may improve risk stratification for patients with incomplete clinicopathological information and may reveal additional risk stratifiers (such as the suggested large-scale CNVs or AR downregulation) for IMTs.
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