TY - JOUR
AB - Despite the recommendations of the latest guidelines, the practical efficacy of universal screening for identifying Lynch syndrome (LS) among patients with colorectal cancer (CRC) may be limited in the real world due to infrequent referrals and the difficulties of genetic testing. Thus, the present study aimed to retrospectively analyze the results of universal screening of patients with CRC at a referral hospital in Japan. Immunohistochemistry was performed for mismatch repair proteins [including DNA mismatch repair protein MSH6 (MSH6), mismatch repair endonuclease PMS2 (PMS2), DNA mismatch repair protein Msh2 (MSH2) and DNA mismatch repair protein Mlh1 (MLH1)] and BRAF V600E mutation. Tumors that showed the following were considered to indicate LS and patients with such tumors were designated as genetic testing candidates (GTCs): i) Loss of MSH6/MSH2; ii) loss of MSH6 alone; iii) loss of PMS2 alone; and iv) loss of PMS2/MLH1 with negative BRAF V600E. MLH1 methylation and BRAF V600E mutation were analyzed in deficient mismatch repair (dMMR) tumors retrospectively. The frequency of dMMR and GTCs in an independent cohort of patients with young‑onset CRC were also investigated. Universal screening revealed dMMR tumors, GTCs and LS probands in 7.3, 3.9 and 0.4%, respectively, of 463 patients with CRC. Although dMMR tumors were observed in both younger (<50 years) and older (≥60 years) patients, the GTCs were enriched in younger individuals. Evaluation of mismatch repair status in an independent cohort confirmed the high rate of GTCs in patients with young‑onset CRC. The low detection rate of LS demonstrated in this study questions the implementation of routine universal screening in regions with low prevalence of LS. Considering the enrichment of GTCs in young‑onset CRCs, age‑restricted strategies may be simple and efficient practical alternatives to universal screening in the real world.
AD - Department of Clinical Oncology, Kyoto University Hospital, Kyoto City, Kyoto 606‑8507, Japan
Department of Diagnostic Pathology, Graduate School of Medicine, Kyoto University, Kyoto City, Kyoto 606‑8507, Japan
Department of Surgery, Kyoto University Hospital, Kyoto City, Kyoto 606‑8507, Japan
Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto City, Kyoto 606‑8507, Japan
Clinical Genetics Unit, Kyoto University Hospital, Kyoto City, Kyoto 606‑8507, Japan
Oncogene Research Unit and Cancer Prevention Unit, Tochigi Cancer Center Research Institute, Utsunomiya, Tochigi 320‑0834, Japan
AU - Yamada,Atsushi
AU - Matsuoka,Yui
AU - Minamiguchi,Sachiko
AU - Yamamoto,Yoshihiro
AU - Kondo,Tomohiro
AU - Sunami,Tomohiko
AU - Horimatsu,Takahiro
AU - Kawada,Kenji
AU - Seno,Hiroshi
AU - Torishima,Masako
AU - Murakami,Hiromi
AU - Yamada,Takahiro
AU - Kosugi,Shinji
AU - Sugano,Kokichi
AU - Muto,Manabu
AU - Yamada,Atsushi
AU - Matsuoka,Yui
AU - Minamiguchi,Sachiko
AU - Yamamoto,Yoshihiro
AU - Kondo,Tomohiro
AU - Sunami,Tomohiko
AU - Horimatsu,Takahiro
AU - Kawada,Kenji
AU - Seno,Hiroshi
AU - Torishima,Masako
AU - Murakami,Hiromi
AU - Yamada,Takahiro
AU - Kosugi,Shinji
AU - Sugano,Kokichi
AU - Muto,Manabu
DA - 2021/12/01
DO - 10.3892/mco.2021.2409
IS - 6
JO - Mol Clin Oncol
KW - Lynch syndrome
universal screening
colorectal cancer
real‑world
young‑onset
PY - 2021
SN - 2049-9450
2049-9469
SP - 247
ST - Real‑world outcome of universal screening for Lynch syndrome in Japanese patients with colorectal cancer highlights the importance of targeting patients with young‑onset disease
T2 - Molecular and Clinical Oncology
TI - Real‑world outcome of universal screening for Lynch syndrome in Japanese patients with colorectal cancer highlights the importance of targeting patients with young‑onset disease
UR - https://doi.org/10.3892/mco.2021.2409
VL - 15
ER -