Preoperative Screening of Colorectal Cancers Is As Accurate As Postoperative Screening for Detection of Lynch Syndrome

Harrigan, Jack; Davis, Christian; Chauhan, Mahak; Buckles, Daniel; Saeed, Anwaar; Kennedy, Kevin; Collins, Debra L.; Olyaee, Mojtaba; Madan, Rashna; Bansal, Ajay

doi:10.1016/j.cgh.2020.05.016

Clinical Gastroenterology and Hepatology

2020

DOI: 10.1016/j.cgh.2020.05.016

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Preoperative Screening of Colorectal Cancers Is As Accurate As Postoperative Screening for Detection of Lynch Syndrome

Jack Harrigan

Christian Davis

Mahak Chauhan

et al.

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Cited by 2 publications

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Mismatch repair deficiency: how reliable is the two‐antibody approach? A national real‐life study

Vink‐Börger,

den Bakker,

Voorham

et al. 2024

Histopathology

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AimsTraditionally, mismatch repair (MMR) status is determined by a panel of four antibodies (MLH1, PMS2, MSH2, MSH6). If all proteins are retained, cases are MMR proficient (pMMR), while loss of one or more proteins is indicative of MMR deficiency (dMMR). This approach has been challenged in favour of a two‐antibody approach, using PMS2 and MSH6 as a first screening. Their retainment is deemed sufficient to declare cases pMMR. In this study we aim to verify the validity of the two‐antibody approach.Methods and ResultsWe performed a nationwide study in colorectal cancer (CRC) and endometrial cancer (EC) diagnosed between 2016 and 2023, including 47,657 patients to evaluate the two‐antibody approach. In 0.17% and 0.4% of cases of CRC and EC, respectively, dMMR cases would be missed with the two‐antibody approach. Subgroup analyses pointed towards slightly increased miss rates in younger patients (under the age of 50 years) in both groups and identified special subtypes (signet ring cell carcinoma, medullary carcinoma, and mucinous carcinoma in CRC and clear cell carcinoma in EC) with increased miss rates. For these specific subgroups, a low threshold should be used for further testing. In case of ambiguous or heterogeneous staining patterns, four antibodies should be used.ConclusionIn general, the application of a two‐antibody MMR testing strategy does not lead to considerable failure of dMMR identification and saves costs.

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Mismatch repair deficiency: how reliable is the two‐antibody approach? A national real‐life study

Vink‐Börger,

den Bakker,

Voorham

et al. 2024

Histopathology

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Identifying patients with Lynch syndrome using a universal tumor screening program in an integrated healthcare system

Crain

Zepp

Gille

et al. 2022

Hered Cancer Clin Pract

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Introduction Lynch syndrome (LS) is associated with an increased risk of colorectal (CRC) and endometrial (EC) cancers. Universal tumor screening (UTS) of all individuals diagnosed with CRC and EC is recommended to increase identification of LS. Kaiser Permanente Northwest (KPNW) implemented a UTS program for LS among individuals newly diagnosed with CRC in January 2016 and EC in November 2016. UTS at KPNW begins with immunohistochemistry (IHC) of tumor tissue to determine loss of mismatch repair proteins associated with LS (MLH1, MSH2, MSH6, and PMS2)., IHC showing loss of MLH1 is followed by reflex testing (automatic testing) to detect the presence of the BRAF V600E variant (in cases of CRC) and MLH1 promoter hypermethylation to rule out likely sporadic cases. Materials and methods Individuals newly diagnosed with CRC and EC were identified between the initiation of the respective UTS programs and July 2018. Electronic medical records were reviewed to extract patient data related to UTS, including IHC and reflex testing results, date of referrals to the genetics department, and results of germline genetic testing for LS. Results 313 out of 362 individuals diagnosed with CRC and 61 out of 64 individuals diagnosed with EC who were eligible were screened by IHC for LS. Most (47/52 or 90%, including 46/49 CRC and 1/3 EC) individuals that were not screened by IHC only had a biopsy sample available. Fourteen individuals (3.7% overall, including 13/313 CRC and 1/61 EC) received an abnormal result after reflex testing and were referred for genetic counseling. Of these, 10 individuals (71% overall, including 9/13 CRC and 1/1 EC) underwent germline genetic testing for LS. Five individuals diagnosed with CRC were found to have pathogenic variants. in PMS2 (n = 3), MLH1 (n = 1), and MSH6 (n = 1). No pathogenic variants were identified in individuals diagnosed with EC. Conclusions UTS identified individuals at risk for LS. Most individuals who screened positive for LS had follow-up germline genetic testing for LS. The consistent use of biopsy samples is an opportunity to improve UTS.

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Preoperative Screening of Colorectal Cancers Is As Accurate As Postoperative Screening for Detection of Lynch Syndrome

Cited by 2 publications

References 7 publications

Mismatch repair deficiency: how reliable is the two‐antibody approach? A national real‐life study

Mismatch repair deficiency: how reliable is the two‐antibody approach? A national real‐life study

Identifying patients with Lynch syndrome using a universal tumor screening program in an integrated healthcare system

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