Cancer Res Treat.  2023 Jan;55(1):179-188. 10.4143/crt.2021.1512.

Universal Screening for Lynch Syndrome Compared with Pedigree-Based Screening: 10-Year Experience in a Tertiary Hospital

• Kim MH
• Kim DW
• Lee HS
• Bang SK
• Seo SH
• Park KU
• Oh HK
• Kang SB

• KMID: 2538003
• DOI: http://doi.org/10.4143/crt.2021.1512

Abstract

Purpose
Universal screening for Lynch syndrome (LS) refers to routine tumor testing for microsatellite instability (MSI) among all patients with colorectal cancer (CRC). Despite its widespread adoption, real-world data on the yield is lacking in Korean population. We studied the yield of adopting universal screening for LS in comparison with pedigree-based screening in a tertiary center.
Materials and Methods
CRC patients from 2007-2018 were reviewed. Family histories were obtained and were evaluated for hereditary nonpolyposis colorectal cancer (HNPCC) using Amsterdam II criteria. Tumor testing for MSI began in 2007 and genetic testing was offered using all available clinicopathologic data. Yield of genetic testing for LS was compared for each approach and step.
Results
Of the 5,520 patients, tumor testing was performed in 4,701 patients (85.2%) and family histories were obtained from 4,241 patients (76.8%). Hereditary CRC (LS or HNPCC) was present in 69 patients (1.3%). MSI-high was present in 6.9%, and 25 patients had confirmed LS. Genetic testing was performed in 41.2% (47/114) of MSI-high patients, out of which 40.4% (19/47) were diagnosed with LS. There were six additional LS patients found outside of tumor testing. For pedigree-based screening, Amsterdam II criteria diagnosed 55 patients with HNPCC. Fifteen of these patients underwent genetic testing, and 11 (73.3%) were diagnosed with LS. Two patients without prior family history were diagnosed with LS and relied solely on tumor testing results.
Conclusion
Despite widespread adoption of routine tumor testing for MSI, this is not a fail-safe approach to screen all LS patients. Obtaining a thorough family history in combination with universal screening provides a more comprehensive ‘universal’ screening method for LS.

Keyword

Colorectal neoplasms; Family history; Hereditary nonpolyposis colorectal cancer; Lynch syndrome; Pedigree; Universal screening

Figure

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  Fig. 1 Disposition of colorectal cancer patients who received diagnoses of Lynch syndrome. HNPCC, hereditary nonpolyposis colorectal cancer; IHC, immunohistochemistry; MMR, mismatch repair; MSI-H, microsatellite instability high; MSI-L, microsatellite instability low.

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  Fig. 2 Diagnosis of Lynch syndrome by universal screening. MSI-H, microsatellite instability high; MSI-L, microsatellite instability low; MSS, microsatellite stable.

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  Fig. 3 Diagnosis of Lynch syndrome by pedigree-based screening. MSI, microsatellite instability.

Reference

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