Patients with unexplained mismatch repair deficiency are interested in updated genetic testing

Abstract Background Individuals who have colorectal or endometrial cancers displaying loss of immunohistochemical staining of one or more mismatch repair proteins without an identifiable causative germline pathogenic variant have unexplained mismatch repair deficiency (UMMRD). Comprehensive germline genetic testing for Lynch syndrome (LS) includes sequencing and deletion/duplication analysis of MLH1, MSH2, MSH6, and PMS2, deletion analysis of EPCAM, and MSH2 inversion analysis. Updated genetic testing to include elements of comprehensive LS testing not previously completed could further clarify LS status in individuals with UMMRD, allowing for tailored screening guidelines for affected individuals and their family members. However, patient understanding of the potential impact of updated genetic testing for LS is unclear. This study aimed to evaluate the interest in and perceived impact of updated genetic testing among individuals with UMMRD at a tertiary academic center. Methods A survey evaluating interest in and perceived impact of updated genetic testing was mailed to 98 potential participants. Electronic health record review was completed for all individuals meeting eligibility criteria. Thirty-one individuals responded to the survey. Results Results indicate this population is highly interested in updated genetic testing with the perceived impact being primarily for family members to have appropriate genetic testing and screening. Electronic health record review indicates that clinicians have an evolving understanding of causes of UMMRD, representing a potential change in assessment of cancer risk. Conclusions Updated risk assessment and genetic counseling with a discussion of the benefits and limitations of germline and somatic genetic testing, is essential as the understanding of UMMRD and genetic testing recommendations for this population evolve.

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Computers in the examination room and the electronic health record: physicians' perceived impact on clinical encounters before and after full installation and implementation

Family Practice ◽

10.1093/fampra/cms015 ◽

2012 ◽

Vol 29 (5) ◽

pp. 601-608 ◽

Cited By ~ 43

Author(s):

Richard J Doyle ◽

Nina Wang ◽

David Anthony ◽

Jeffrey Borkan ◽

Renee R Shield ◽

...

Keyword(s):

Electronic Health Record ◽

Health Record ◽

Clinical Encounters ◽

Before And After ◽

Perceived Impact ◽

Electronic Health ◽

Examination Room

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Retroactive assessment for DNA mismatch repair deficiency in women with a history of endometrial cancer

Medical Research Archives ◽

10.18103/mra.v9i4.2349 ◽

2021 ◽

Vol 9 (4) ◽

Author(s):

Y. Chen ◽

Sushmita Gordhandas ◽

Kelsey Musselman ◽

Zhen Zhou ◽

Brandon Maddy ◽

...

Keyword(s):

Endometrial Cancer ◽

Genetic Counseling ◽

Genetic Testing ◽

Mismatch Repair ◽

Gynecologic Oncology ◽

Molecular Classification ◽

Pathogenic Mutation ◽

Mismatch Repair Deficiency ◽

Repair Deficiency ◽

Mismatch Repair Proteins

Objectives. Beginning in 2014, the Society of Gynecologic Oncology and the American College of Obstetricians and Gynecologists have recommended universal tumor testing for mismatch repair deficiency in endometrial cancer. Mismatch repair testing can triage patients who may benefit from genetic testing for Lynch syndrome. Many women previously diagnosed with endometrial cancer have not undergone mismatch repair tumor testing. We sought to determine the feasibility of retroactive assessment for mismatch repair deficiency among women with diagnosed with endometrial cancer prior to 2014. Methods. Between 2016 and 2018, we identified 36 patients presenting for gynecologic oncology follow-up visits who were previously diagnosed with endometrial cancer. The endometrial pathology underwent tumor assessment for loss of expression of mismatch repair proteins by immunohistochemistry. Patients with abnormal mismatch repair testing were referred to genetic counseling and, if indicated, for germline genetic testing. Results. Thirty-six patients underwent retroactive tumor immunohistochemistry, yielding 10 (28%) abnormal results, including nine (25%) with loss of one or more mismatch repair proteins and one with inconclusive staining (2.8%). All ten patients with abnormal immunohistochemistry were referred to genetic counseling; 9 (90%) accepted the referral and proceeded with genetic testing. One pathogenic mutation was identified in CHEK2 (11%). Five patients (56%) were found to have a variant of unknown significance. Conclusions. Implementation of universal retroactive tumor testing for mismatch repair deficiency in patients previously diagnosed with endometrial cancer is feasible. With the growing use of new molecular classification protocols for endometrial tumors, identification of mismatch repair deficiency may have significant clinicopathologic implications.

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