ArticleJournal of clinical oncology : official journal of the American Society of Clinical Oncology2014
Tumor mismatch repair immunohistochemistry and DNA MLH1 methylation testing of patients with endometrial cancer diagnosed at age younger than 60 years optimizes triage for population-level germline mismatch repair gene mutation testing.
Article in Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers, 4 of them syntheses that pooled it.
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Who cites it
106 citing papers in PubMed, 4 syntheses or guidelines pooled it, 215 citations in OpenAlex.
- Testing strategies for Lynch syndrome in people with endometrial cancer: systematic reviews and economic evaluation.Health technology assessment (Winchester, England) · 2021Pooled it
- Guideline
- The proportion of endometrial cancers associated with Lynch syndrome: a systematic review of the literature and meta-analysis.Genetics in medicine : official journal of the American College of Medical Genetics · 2019Pooled it
- AGO Austria recommendation on screening and diagnosis of Lynch syndrome (LS).Archives of gynecology and obstetrics · 2017Guideline
- Clinical activity of durvalumab for patients with advanced mismatch repair-deficient and repair-proficient endometrial cancer. A nonrandomized phase 2 clinical trial.Journal for immunotherapy of cancer · 2021Trial
- Genetic Variation ofInternational journal of dentistry · 2026Article
- Review
- Methylation-sensitive high-resolution melting technology is a simple and sensitive method to detect germline epimutation of the MLH1 gene promoter.Clinical epigenetics · 2025Article
- Clinical Molecular Immunohistochemistry Mismatch Repair Mutations in Lynch Syndrome in Patients Under 50 Years: A Systematic Review.Biomedicines · 2025Review
- Production and Role of Nitric Oxide in Endometrial Cancer.Antioxidants (Basel, Switzerland) · 2025Review
- Lynch Syndrome-Impact of the Type of Deficient Mismatch Repair Gene Mutation on Diagnosis, Clinical Presentation, Surveillance and Therapeutic Approaches.Medicina (Kaunas, Lithuania) · 2025Review
- Unveiling pembrolizumab effectiveness in diverse subtypes of MSI-high endometrial cancers.Journal of gynecologic oncology · 2024Article
- Using Genetics to Investigate Relationships between Phenotypes: Application to Endometrial Cancer.Genes · 2024Review
- Article
- Clinical features and impact of p53 status on sporadic mismatch repair deficiency and Lynch syndrome in uterine cancer.Cancer science · 2024Article
- Intratumoral presence of the genotoxic gut bacteria pksBritish journal of cancer · 2024Article
- Microsatellite Instability Is Insufficiently Used as a Biomarker for Lynch Syndrome Testing in Clinical Practice.JCO precision oncology · 2024Article
- Comparison of immediate germline sequencing and multi-step screening for Lynch syndrome detection in high-risk endometrial and colorectal cancer patients.Journal of gynecologic oncology · 2024Article
- Article
- Article
46 more citing papers are in PubMed but not listed here.
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22 authors at 1 institution in 1 country.
Funding
Abstract
purposeClinicopathologic data from a population-based endometrial cancer cohort, unselected for age or family history, were analyzed to determine the optimal scheme for identification of patients with germline mismatch repair (MMR) gene mutations. PATIENTS AND
methodsEndometrial cancers from 702 patients recruited into the Australian National Endometrial Cancer Study (ANECS) were tested for MMR protein expression using immunohistochemistry (IHC) and for MLH1 gene promoter methylation in MLH1-deficient cases. MMR mutation testing was performed on germline DNA of patients with MMR-protein deficient tumors. Prediction of germline mutation status was compared for combinations of tumor characteristics, age at diagnosis, and various clinical criteria (Amsterdam, Bethesda, Society of Gynecologic Oncology, ANECS).
resultsTumor MMR-protein deficiency was detected in 170 (24%) of 702 cases. Germline testing of 158 MMR-deficient cases identified 22 truncating mutations (3% of all cases) and four unclassified variants. Tumor MLH1 methylation was detected in 99 (89%) of 111 cases demonstrating MLH1/PMS2 IHC loss; all were germline MLH1 mutation negative. A combination of MMR IHC plus MLH1 methylation testing in women younger than 60 years of age at diagnosis provided the highest positive predictive value for the identification of mutation carriers at 46% versus ≤ 41% for any other criteria considered.
conclusionPopulation-level identification of patients with MMR mutation-positive endometrial cancer is optimized by stepwise testing for tumor MMR IHC loss in patients younger than 60 years, tumor MLH1 methylation in individuals with MLH1 IHC loss, and germline mutations in patients exhibiting loss of MSH6, MSH2, or PMS2 or loss of MLH1/PMS2 with absence of MLH1 methylation.
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