scholarly journals 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

2021 ◽  
Vol 15 (6) ◽  
Author(s):  
Atsushi Yamada ◽  
Yui Matsuoka ◽  
Sachiko Minamiguchi ◽  
Yoshihiro  Yamamoto ◽  
Tomohiro  Kondo ◽  
...  
2020 ◽  
Author(s):  
George Kunnackal John ◽  
Vipin Das Villgran ◽  
Christine Caufield-Noll ◽  
Francis Giardiello

2017 ◽  
Vol 16 (3) ◽  
pp. 377-387 ◽  
Author(s):  
Jessica Ezzell Hunter ◽  
Kathleen A. Arnold ◽  
Jennifer E. Cook ◽  
Jamilyn Zepp ◽  
Marian J. Gilmore ◽  
...  

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 41-41
Author(s):  
Yasuaki Yamamoto ◽  
Yuichiro Tsukada ◽  
Takeshi Kuwata ◽  
Motohiro Kojima ◽  
Yumie Hiraoka ◽  
...  

41 Background: Universal screening for Lynch syndrome (LS) by identifying deficient DNA mismatch repair (MMR) in the tumor tissue of all new colorectal cancer (CRC) patients is widely accepted. The population prevalence of LS is approximately 3% in Western countries, whereas it is approximately 0.7% in Japan. In addition, the number of relatives diagnosed per proband is 3.6 in Western countries, whereas there are even fewer diagnoses per proband in Japan. To address the issue of LS remaining largely underdiagnosed in Japan, we prospectively evaluated the clinical utility of universal screening of LS in CRC patients. Methods: From March 2016 to August 2019, all consecutive new cases of stage II/III CRC underwent immunohistochemistry (IHC) screening for MMR using MLH1, MSH2, MSH6, and PMS2 antibodies. The patients negative for both MLH1 and PMS2 (MLH1-/PMS2-) were subjected to reflex testing for BRAF V600E mutation. Patients with both MLH1-/PMS2- and BRAF negative (cohort A, n = 14) and those with other IHC patterns (cohort B, n = 13) were referred for genetic counseling (GC) and genetic testing (GT). Furthermore, relatives of probands with confirmed LS were referred for GC/GT if they were willing. Results: Overall, 591 pts were enrolled in this study. Patient background were as follows: > 70 y/o, 35%; right-sided/left-sided colon/rectum, 24%/24%/53%; and cStage II/III, 65%/35%. Of 591 patients, 40 (6.8%) had MMR deficiency. Of 27 patients with MLH1-/PMS2-, 24 underwent BRAF reflex testing; only 10 of these patients tested positive for mutation. Of 27 patients recommended for GC, 25 were referred for GC and 22 for GT, which revealed 12 LS cases (2%, mutation genes:MLH1/PMS2/MSH2; 4/2/6). The frequency of LS diagnosis with respect to patient background was as follows: > 70/≤70 y, 1.0/2.6%; right-sided/left-sided colon/rectum, 5.8/0/1.3%; and cStage II/III, 2.6/1.0%. Interestingly, only 3 (25%) of 12 patients who underwent GC/GT in cohort A had LS compared with 9 (90%) of 10 patients in cohort B ( p= 0.004). Moreover, among 11 relatives of 5 families who were willing to undergo GC/GT, six (55%) had LS, of whom two were first-degree relatives (33%), one was a second-degree relative (50%), and three were third-degree relatives (100%). Conclusions: This study showed that universal screening of LS in CRC patients is significantly useful in Japan. Furthermore, implementing a reflex testing strategy demonstrated high adherence to guidelines and the appropriateness of our referrals for GC/GT.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1512-1512 ◽  
Author(s):  
Jeffrey M. Goldberg ◽  
Andrea L. Lewis ◽  
Michelle Alabek ◽  
Cara Dreher ◽  
Sandra Elane Brooks

1512 Background: Identification of colorectal cancer (CRC) cases that are due to Lynch Syndrome (LS) is important to prevent secondary malignancies or development of additional malignancies among relatives. Utilization of clinical criteria to select CRC patients for laboratory testing fails to identify a significant proportion of patients whose CRC is due to LS. Therefore, universal screening for LS among CRC patients has been advocated by the Evaluation of Genomic Applications in Practice and Prevention Working Group. However, the feasibility of routine universal screening has not been evaluated in a community-based, non-research setting. We implemented a universal screening protocol for LS as part of routine care of CRC at Norton Healthcare, a multi-institutional community-based healthcare organization. Methods: Beginning in October 2009, all resected CRC tumors automatically underwent immunohistochemistry analysis (IHC) for Lynch Syndrome-associated mismatch repair gene (MMR) expression. Selected patients who underexpressed MLH1 also underwent testing for the BRAF V600E mutation. Patients who had a BRAF V600E mutation were considered to have sporadic CRC. All other patients with abnormal IHC were automatically referred for genetic counseling. We retrospectively reviewed the outcomes of genetic counseling in all patients referred through this universal screening protocol. Results: Between October 2009 and December 2011, 388 patients underwent resection of CRC, all of whom had IHC for MMR expression. Seventy patients were identified as having abnormal IHC. Sixty-two had MLH1/PMS2 underexpression, of which 18 underwent BRAF testing and 13 had a BRAF V600E mutation. Eight had MSH2/MSH6 underexpression. Nine patients have been confirmed to have LS, 31 have been found not to have LS, and 19 are in the process of evaluation. Seven patients declined genetic counseling, and 4 died before they could be adequately evaluated. Conclusions: Universal screening for CRC due to LS, using IHC with select BRAF V600E mutation testing and automated referral for genetic counseling, is feasible in the community setting. Funded in part with federal funds: NCI, NIH, Contract No. HHSN261200800001.


2015 ◽  
Vol 17 (9) ◽  
pp. 787-793 ◽  
Author(s):  
D. Stupart ◽  
A. K. Win ◽  
I. M. Winship ◽  
M. Jenkins

2018 ◽  
Vol 154 (6) ◽  
pp. S-791-S-792
Author(s):  
George Kunnackal John ◽  
Vipin D. Villgran ◽  
Christine Caufield-Noll ◽  
Francis Giardiello

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