Clinicopathologic features of endometrial cancer with mismatch repair deficiency
Kahn, Ryan M.
Baltich Nelson, Becky
Christos, Paul J.
Caputo, Thomas A.
Frey, Melissa K.
UMass Chan AffiliationsLamar Soutter Library
Document TypeJournal Article
DNA mismatch repair
MutL protein homolog 1
MutS homolog 2 protein
epithelial cell adhesion molecule
mismatch repair endonuclease PMS2
Amino Acids, Peptides, and Proteins
Female Urogenital Diseases and Pregnancy Complications
Obstetrics and Gynecology
MetadataShow full item record
AbstractThe inclusion of DNA mismatch repair (MMR) evaluation as a standard of care for endometrial cancer management will result in a growing population of patients with MMR deficiency and negative germline Lynch syndrome testing (MMR-deficient). In this systematic review and study, the clinicopathologic features of endometrial cancer in patients with MMR-intact, MLH1 methylation positive, MMR-deficient or Lynch syndrome are evaluated. A systematic search of online databases between 1990 and 2018 identified studies of endometrial cancer patients with tumour testing (MMR protein immunohistochemistry or microsatellite instability) and germline assessment for Lynch syndrome. Extracted data included tumour testing, germline genetic testing, age, body mass index (BMI), family history, tumour stage, grade and histologic type. Associations between MMR-intact, MLH1 methylation positive, MMR-deficient and Lynch syndrome groups were analysed using descriptive statistics. The comprehensive search produced 4,400 publications, 29 met inclusion criteria. A total of 7,057 endometrial cancer cases were identified, 1,612 with abnormal immunohistochemistry, 977 with microsatellite instability. Nine-hundred patients underwent germline genetic testing, identifying 212 patients with Lynch syndrome. Patients in the Lynch syndrome and MMR-deficient groups were significantly younger than patients in the MMR-intact and MLH1 methylation positive groups. Patients with MMR-intact tumours had the highest BMI, followed by MMR-deficient, then Lynch syndrome. MMR-intact tumours were more likely to be grade I at diagnosis than other groups. Patients with Lynch syndrome and MMR-deficient tumours were less likely to have stage I disease as compared to patients with MMR-intact tumours. Endometrial cancer patients with MMR-deficient tumours have similar features to those with germline Lynch syndrome mutations, including age, grade, histology and stage. Even in the absence of a germline mutation, tumour evaluation for MMR status may have important clinical implications.
Gordhandas S, Kahn RM, Gamble C, Talukdar N, Maddy B, Nelson BB, Askin G, Christos PJ, Holcomb K, Caputo TA, Chapman-Davis E, Frey MK. Clinicopathologic features of endometrial cancer with mismatch repair deficiency. Ecancermedicalscience. 2020 Jun 18;14:1061. doi: 10.3332/ecancer.2020.1061. PMID: 32582376; PMCID: PMC7302890. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/41503
RightsCopyright © the authors; licensee ecancermedicalscience. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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