ArticleCurrent pharmaceutical design2014
Utility of MLH1 methylation analysis in the clinical evaluation of Lynch Syndrome in women with endometrial cancer.
Article in Current pharmaceutical design, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 45 citations in OpenAlex.
- Article
- Context-dependent environmental associations with endometrial cancer histotype and genotype.International journal of gynecological cancer : official journal of the International Gynecological Cancer Society · 2023Article
- Correlation of PD-L1 immunohistochemical expression with microsatellite instability and p53 status in endometrial carcinoma.European journal of obstetrics & gynecology and reproductive biology: X · 2022Article
- The Role of Immunohistochemistry Markers in Endometrial Cancer with Mismatch Repair Deficiency: A Systematic Review.Cancers · 2022Review
- Efficacy of PD-1 Inhibitor Combined with Bevacizumab in Treatment of Advanced Endometrial Cancer Patients with Mismatch Repair Deficiency (dMMR)/High-Level Microsatellite Instability (MSI-H).Medical science monitor : international medical journal of experimental and clinical research · 2022Article
- Article
- Diagnosis of Lynch Syndrome and Strategies to Distinguish Lynch-Related Tumors from Sporadic MSI/dMMR Tumors.Cancers · 2021Review
- How Should We Test for Lynch Syndrome? A Review of Current Guidelines and Future Strategies.Cancers · 2021Review
- Performance characteristics of screening strategies to identify Lynch syndrome in women with ovarian cancer.Cancer · 2020Article
- An Analysis of Clinical, Surgical, Pathological and Molecular Characteristics of Endometrial Cancer According to Mismatch Repair Status. A Multidisciplinary Approach.International journal of molecular sciences · 2020Article
- Clinicopathological significance of deficient DNA mismatch repair and MLH1 promoter methylation in endometrioid endometrial carcinoma.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2020Article
- Clinicopathologic features of endometrial cancer with mismatch repair deficiency.Ecancermedicalscience · 2020Article
- Importance of PCR-based Tumor Testing in the Evaluation of Lynch Syndrome-associated Endometrial Cancer.Advances in anatomic pathology · 2017Review
- Clinical Challenges Associated with Universal Screening for Lynch Syndrome-Associated Endometrial Cancer.Cancer prevention research (Philadelphia, Pa.) · 2017Article
- 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.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2014Article
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Clinical screening criteria, such as young age of endometrial cancer diagnosis and family history of signature cancers, have traditionally been used to identify women with Lynch Syndrome, which is caused by mutation of a DNA mismatch repair gene. Immunohistochemistry and microsatellite instability analysis have evolved as important screening tools to evaluate endometrial cancer patients for Lynch Syndrome. A complicating factor is that 15-20% of sporadic endometrial cancers have immunohistochemical loss of the DNA mismatch repair protein MLH1 and high levels of microsatellite instability due to methylation of MLH1. The PCR-based MLH1 methylation assay potentially resolves this issue, yet many clinical laboratories do not perform this assay. The objective of this study was to determine if clinical and pathologic features help to distinguish sporadic endometrial carcinomas with MLH1 loss secondary to MLH1 methylation from Lynch Syndrome-associated endometrial carcinomas with MLH1 loss and absence of MLH1 methylation. Of 337 endometrial carcinomas examined, 54 had immunohistochemical loss of MLH1. 40/54 had MLH1 methylation and were designated as sporadic, while 14/54 lacked MLH1 methylation and were designated as Lynch Syndrome. Diabetes and deep myometrial invasion were associated with Lynch Syndrome; no other clinical or pathological variable distinguished the 2 groups. Combining Society of Gynecologic Oncology screening criteria with these 2 features accurately captured all Lynch Syndrome cases, but with low specificity. In summary, no single clinical/pathologic feature or screening criteria tool accurately identified all Lynch Syndrome-associated endometrial carcinomas, highlighting the importance of the MLH1 methylation assay in the clinical evaluation of these patients.
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