ArticleThe journal of pathology. Clinical research2015
Loss of ATRX and DAXX expression identifies poor prognosis for smooth muscle tumours of uncertain malignant potential and early stage uterine leiomyosarcoma.
Article in The journal of pathology. Clinical research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- Alternative lengthening of telomeres (ALT) influences survival in soft tissue sarcomas: a systematic review with meta-analysis.BMC cancer · 2019Pooled it
- Genomic insights into uterine leiomyosarcoma: Unraveling KMT2D, CREBBP, NOTCH2, TSC2, ATM, and GNAS signatures.Clinics (Sao Paulo, Brazil) · 2026Article
- The Evolving Molecular Landscape of Uterine Mesenchymal Tumors: Diagnostic and Therapeutic Implications.Cancers · 2025Review
- Context is key: how diagnostic and prognostic markers are reshaping gynecologic pathology.The journal of pathology. Clinical research · 2025Review
- Review
- Challenges Associated with Smooth Muscle Tumor of Uncertain Malignant Potential (STUMP) Management-A Case Report with Comprehensive Literature Review.Journal of clinical medicine · 2024Review
- Uterine smooth muscle tumors of uncertain malignant potential: a 13-year retrospective study.Frontiers in oncology · 2024Article
- Review
- Molecular-Based Immunohistochemical Algorithm for Uterine Leiomyosarcoma Diagnosis.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2023Article
- Increased Expression of the Δ133p53β Isoform Enhances Brain Metastasis.International journal of molecular sciences · 2023Article
- Risk of Recurrence in Uterine Leiomyoma with Bizarre Nuclei: a Systematic Review and Meta-Analysis.Geburtshilfe und Frauenheilkunde · 2021Article
- Review
- ATRX Alteration Contributes to Tumor Growth and Immune Escape in Pleomorphic Sarcomas.Cancers · 2021Article
- Genome wide methylation profiling of selected matched soft tissue sarcomas identifies methylation changes in metastatic and recurrent disease.Scientific reports · 2021Article
- The Role of Alternative Lengthening of Telomeres Mechanism in Cancer: Translational and Therapeutic Implications.Cancers · 2020Review
- Liquid Biopsy as a Tool for Differentiation of Leiomyomas and Sarcomas of Corpus Uteri.International journal of molecular sciences · 2019Review
- A Comparison of Death Domain-Associated Protein 6 in Different Endometrial Carcinomas Histotypes.Biomarker insights · 2019Article
- Integrated genetic and epigenetic analysis of myxofibrosarcoma.Nature communications · 2018Article
- Exome Sequencing of Uterine Leiomyosarcomas Identifies Frequent Mutations in TP53, ATRX, and MED12.PLoS genetics · 2016Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Uterine smooth muscle tumours of uncertain malignant potential (STUMP) are diagnostically and clinically challenging. The alternative lengthening of telomeres (ALT) telomere maintenance mechanism is associated with poor survival in soft tissue leiomyosarcoma. Time to first recurrence and survival were known for 18 STUMP and 43 leiomyosarcomata (LMS). These were screened for ALT telomere maintenance by the presence of ALT-associated PML bodies (APBs) and for changes associated with the ALT phenotype, namely aberrant p53 expression, isocitrate dehydrogenase 1 mutation (R132H substitution) expression, mutant ATRX (αthalassemia/mental retardation syndrome X-linked) expression and mutant DAXX (death-domain-associated protein) expression by immunohistochemistry (IHC). Overexpression of p16(INK4A) was examined immunohistologically in a subset of cases. Many of the tumours associated with death or recurrence demonstrated APBs commensurate with ALT telomere maintenance. However, all uterine STUMP (4/4), and vaginal STUMP (2/2) patients, and almost all LMS patients (88.4%, 23/26, including 90% (9/10) of stage 1 LMS cases), who had died of disease or who had recurrent disease, displayed loss of ATRX or DAXX expression. Loss of ATRX or DAXX expression identified poor prognosis (95% CI 2.1 to 40.8, p < 0.003), in the LMS group. Thus, loss of ATRX or DAXX expression in uterine smooth muscle tumours identifies a clinically aggressive molecular subtype of early stage LMS and when histopathological features are problematic such as in STUMP. As ATRX and DAXX IHC is readily performed in diagnostic laboratories these are potentially useful for routine histopathological classification and management.
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