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INTRODUCTION: Universal screening of colorectal and uterine cancers is an effective strategy for diagnosis of Lynch syndrome, but the utility of testing for Lynch syndrome in older patients remains unclear. METHODS: We conducted a single- center study in which all patients with a diagnosis of colorectal or uterine cancer between January 1, 2016 to June 30th, 2018 were included. Specialized text-based search of the pathology lab information systems identified the patients. To capture all patients, the search results were tallied with the local cancer center database. A structured RedCap electronic database was created to systematically collect data about demographics, PREMM scores, genetic testing and a detailed 3-generation family pedigree. All patients underwent screening for lynch syndrome using immunohistochemical or microsatellite instability-based testing. Final diagnosis of Lynch syndrome in patients with abnormal screening was based on well- established commercial assays. The yield of Lynch syndrome was compared across five age groups: ≤50, 50–59, 60–69, 70–79, and >80. Statistical analysis was performed using ANOVA and Student's T-test. RESULTS: Of a total of 737 patients with either colorectal or uterine cancer (demographics shown in Table 1), the final diagnosis of Lynch syndrome was made in 2.7% (20/737). As Table 2 shows, 90% of the patients diagnosed to have Lynch syndrome were under 60 years of age. The two cases of Lynch syndrome in the age groups 60–69 and 70–79 had PREMM scores of >5%. All of the colorectal or uterine cancers after age 80 tested negative for Lynch syndrome. CONCLUSION: Screening of colorectal or uterine cancers for Lynch syndrome should be limited to patients less than age 60 or with abnormal PREMM scores in patients >60. Lynch screening should not be performed after age 80. If confirmed by further studies, our results could further streamline the current recommendation of universal screening of all colorectal and uterine cancers for Lynch syndrome and lead to cost savings.

INTRODUCTION: The Prediction Model for Gene Mutations (PREMM) is a widely used tool for predicting the probability of Lynch syndrome but the predictive power of various cutoffs for the risk scores is unclear. METHODS: In this retrospective, single-center study, all patients with a diagnosis of colorectal or uterine cancer between January 1, 2016 and June 30th, 2018 were included. The patients were identified using specialized text-based search of the pathology lab information systems. Additionally, the search results were tallied with the local NCI-designated cancer center database to capture all patients with colon cancer. A structured RedCap electronic database was created to systematically abstract data about demographics, location and stage of colon cancer, PREMM5 scores, genetic testing and a detailed 3-generation family pedigree. All patients underwent screening for Lynch syndrome using immunohistochemical or microsatellite instability based testing. Final diagnoses in patients with abnormal screening was based on well-established commercial assays. The yield of Lynch syndrome was compared across three categories of PREMM5 scores: <2.5%, 2.5–4.9%, ≥5%. These scores reflect pre-test probability of Lynch syndrome. Statistical comparisons were performed using ANOVA. RESULTS: Of a total of 737 patients with either colon or uterine cancer, the final diagnosis of Lynch syndrome was made in 2.8% (21/737). The mean age at the time of cancer diagnosis across the three PREMM categories (<2.5%, 2.5–4.9%, ≥5%) was progressively lower: 68.9 ± 9.0 vs. 54.7 ± 9.5 vs. 48.2 ± 15.2, P < 0.001. Table 1 outlines the characteristics of the three groups. Table 2 describes the performance characteristics of different cutoffs of PREMM5 criteria. CONCLUSION: In patients with colorectal or uterine cancers, PREMM cutoff value of 2.5% identified the majority of patients with Lynch syndrome with a modest increase in the number needed to screen. Therefore, a PREMM score of 2.5% should trigger genetic testing.

INTRODUCTION: Multigene panels are commonly used for genetic testing when Lynch syndrome is suspected. However, the data about the relative yield of Lynch vs. non-Lynch mutations are sparse. METHODS: In this retrospective, single-center study, all patients with a diagnosis of colon or uterine cancer between January 1, 2016 and June 30th, 2018 were included. The patients were identified using search in the pathology database for SNOMED codes. Additionally, the search results of SNOMED codes were tallied with the cancer center database to capture all patients with colon cancer. A structured RedCap electronic database was created to systematically abstract data about demographics, location and stage of colon cancer, PREMM5 scores, genetic testing and a detailed 3-generation family pedigree. After being screened for Lynch syndrome using immunohistochemical assays or PCR-based detection of microsatellite instability, patients with abnormal results underwent genetic testing using well-established multi-gene commercial assays. The yields of Lynch and non-Lynch syndromes were compared. Statistical comparisons were performed using Chi-square test for categorical variables and Student's t-test for numerical variables. RESULTS: A total of 737 participants (whites 84.1%, mean age of 62.7) were included. A diagnosis of Lynch syndrome was made in 21 of the 737 participants (2.85%). Non-Lynch mutations were detected in 12 of the 737 participants (1.63%). When colon and uterine cancers were analyzed separately, non-Lynch mutations were detected in 2.1% and 1.5% of participants respectively (Table 1). The non-Lynch genetic mutations detected included: APC, MAP syndrome, CHEK2, BRCA1, BRCA2, MUTYH, PALB2, AXIN2, SMARC4, and NTLH1. CONCLUSION: Germline testing has a significant yield of non-Lynch mutations in patients suspected to have Lynch syndrome. Our data support the current practice of multigene panels to define syndromic cancer risk.

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