ArticleModern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc2019
Quantitative next-generation sequencing-based analysis indicates progressive accumulation of microsatellite instability between atypical hyperplasia/endometrial intraepithelial neoplasia and paired endometrioid endometrial carcinoma.
Article in Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 28 citations in OpenAlex.
- Analysis of racial differences in HER2 status and molecular subtype in grade 3 endometroid endometrial carcinoma.Gynecologic oncology reports · 2025Article
- Impact of molecular and immune signature on endometrial biopsies with atypical hyperplasia with and without concurrent endometroid carcinoma.Gynecologic oncology reports · 2025Article
- Traditional and New Views on MSI-H/dMMR Endometrial Cancer.Biomolecules · 2025Review
- Racial differences in endometrial cancer genomics and outcomes using UNCseqGynecologic oncology reports · 2025Article
- Endometrial Atypical Hyperplasia and Risk of Endometrial Cancer.Diagnostics (Basel, Switzerland) · 2024Review
- Review
- The Role of Immunohistochemistry Markers in Endometrial Cancer with Mismatch Repair Deficiency: A Systematic Review.Cancers · 2022Review
- Histopathologic diagnosis of endometrial precancers: Updates and future directions.Seminars in diagnostic pathology · 2022Review
- Circular RNA hsa_circ_0011324 is involved in endometrial cancer progression and the evolution of its mechanism.Bioengineered · 2022Article
- Characterization of Clonal Evolution in Microsatellite Unstable Metastatic Cancers through Multiregional Tumor Sequencing.Molecular cancer research : MCR · 2021Article
- Next-generation sequencing analysis of endometrial screening liquid-based cytology specimens: a comparative study to tissue specimens.BMC medical genomics · 2020Article
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11 authors at 1 institution in 1 country.
Funding
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Abstract
Atypical hyperplasia/endometrial intraepithelial neoplasia is an accepted precursor to endometrioid-type endometrial carcinoma. Mismatch repair-deficient endometrial carcinomas are also known to be a biologically and clinically distinct subset of tumors. However, the development of microsatellite instability in endometrial carcinogenesis has not yet been evaluated by novel next-generation sequencing-based methods. We examined 17 mismatch repair-deficient endometrioid endometrial carcinomas and their paired atypical hyperplasia/endometrial intraepithelial neoplasia precursors using a next-generation sequencing panel with quantitative microsatellite instability detection at 336 loci. Findings were compared to histological features, polymerase chain reaction-based microsatellite instability testing, immunohistochemical expression of mismatch repair proteins, and tumor mutational burden calculations. All 17 endometrial carcinomas and 8/17 atypical hyperplasia/endometrial intraepithelial neoplasia showed microsatellite instability by next-generation sequencing-based testing. Endometrial carcinoma specimens showed significantly more unstable microsatellite loci than paired atypical hyperplasia/endometrial intraepithelial neoplasia (mean: 40.0% vs 19.9 unstable loci, respectively). Out of nine microsatellite-stable atypical hyperplasia/endometrial intraepithelial neoplasia specimens, four showed mismatch repair loss by immunohistochemistry. All atypical hyperplasia/endometrial intraepithelial neoplasia and endometrial carcinoma specimens with microsatellite instability were also mismatch repair-deficient by immunohistochemistry. Tumor mutational burden was significantly greater in endometrial carcinoma than in paired atypical hyperplasia/endometrial intraepithelial neoplasia specimens, and tumor mutational burden was significantly correlated with percent unstable microsatellite loci. Paired atypical hyperplasia/endometrial intraepithelial neoplasia and endometrial carcinoma specimens show progressive accumulation of unstable microsatellite loci following loss of mismatch repair protein expression. Comprehensive next-generation sequencing-based testing of endometrial carcinomas offers new insights into endometrial carcinogenesis and opportunities for improved tumor surveillance, diagnosis, and management.
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