Top

Published in:

01-06-2016 | Original Article

Lower prevalence of Lynch syndrome in colorectal cancer patients in a Japanese hospital-based population

Authors: Kensuke Kumamoto, Hideyuki Ishida, Okihide Suzuki, Yusuke Tajima, Noriyasu Chika, Koki Kuwabara, Keiichiro Ishibashi, Katsuharu Saito, Koji Nagata, Hidetaka Eguchi, Junichi Tamaru, Takeo Iwama

Published in: Surgery Today | Issue 6/2016

Abstract

Purpose

The aim of this study was to investigate the prevalence of Lynch syndrome among Japanese patients with surgically resected colorectal cancer at a single institution.

Methods

Of 616 colorectal cancer patients who underwent surgical operation in our institution from January 2005 to August 2010, immunohistochemistry analyses for mismatch repair proteins (MLH1, MSH2, MSH6, and PMS2) and microsatellite instability (MSI) testing for surgically resected, formalin-fixed paraffin-embedded colorectal cancer specimens from 138 colorectal cancer patients under 60 years of age were undertaken. Hypermethylation of the MLH1 promoter and BRAF mutation were analyzed where necessary.

Results

Seven patients were identified as candidates for genetic testing by mismatch repair protein loss (n = 7) or MSI-H (n = 6). Methylation of MLH1 was detected in one case. Three patients were diagnosed with Lynch syndrome, comprising 2.2 % of the total colorectal cancer patients younger than 60 years of age.

Conclusion

The prevalence of Lynch syndrome among hospital-based diagnosed cancer patients may therefore be lower than expected in Japan compared with Western populations.

Vasen HF. Clinical diagnosis and management of hereditary colorectal cancer syndromes. J Clin Oncol. 2000;18:81S–92S.PubMed

Umar A, Boland CR, Terdiman JP, Syngal S, de la Chapelle A, Rüschoff J, et al. Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst. 2004;96:261–8.CrossRefPubMedPubMedCentral

Hampel H, Frankel WL, Martin E, Arnold M, Khanduja K, Kuebler P, et al. Feasibility of screening for Lynch syndrome among patients with colorectal cancer. J Clin Oncol. 2008;26:5783–8.CrossRefPubMedPubMedCentral

Hampel H, de la Chapelle A. The search for unaffected individuals with Lynch syndrome: do the ends justify the means? Cancer Prev Res (Phila). 2011;4:1–5.CrossRef

Long N, Moore MA, Chen W, Gao CM, Lai MS, Mizoue T, et al. Cancer epidemiology and control in north-East Asia—past, present and future. Asian Pac J Cancer Prev. 2010;11:107–48.PubMed

Heald B, Plesec T, Liu X, Pai R, Patil D, Moline J, et al. Implementation of universal microsatellite instability and immunohistochemistry screening for diagnosing lynch syndrome in a large academic medical center. J Clin Oncol. 2013;31:1336–40.CrossRefPubMed

Pérez-Carbonell L, Ruiz-Ponte C, Guarinos C, Alenda C, Payá A, Brea A, et al. Comparison between universal molecular screening for Lynch syndrome and revised Bethesda guidelines in a large population-based cohort of patients with colorectal cancer. Gut. 2012;61:865–72.CrossRefPubMed

Morrison J, Bronner M, Leach BH, Downs-Kelly E, Goldblum JR, Liu X. Lynch syndrome screening in newly diagnosed colorectal cancer in general pathology practice: from the revised Bethesda guidelines to a universal approach. Scand J Gastroenterol. 2011;46:1340–8.CrossRefPubMed

Loukola A, Eklin K, Laiho P, Salovaara R, Kristo P, Järvinen H, et al. Microsatellite marker analysis in screening for hereditary nonpolyposis colorectal cancer (HNPCC). Cancer Res. 2001;61:4545–9.PubMed

10.

Aaltonen LA, Sankila R, Mecklin JP, Järvinen H, Pukkala E, Peltomäki P, et al. A novel approach to estimate the proportion of hereditary nonpolyposis colorectal cancer of total colorectal cancer burden. Cancer Detect Prev. 1994;18:57–63.PubMed

11.

Houlston RS, Collins A, Slack J, Morton NE. Dominant genes for colorectal cancer are not rare. Ann Hum Genet. 1992;56:99–103.CrossRefPubMed

12.

Furukawa T, Konishi F, Shitoh K, Kojima M, Nagai H, Tsukamoto T. Evaluation of screening strategy for detecting hereditary nonpolyposis colorectal carcinoma. Cancer. 2002;94:911–20.CrossRefPubMed

13.

Chang SC, Lin PC, Yang SH, Wang HS, Liang WY, Lin JK. Taiwan hospital-based detection of Lynch syndrome distinguishes 2 types of microsatellite instabilities in colorectal cancers. Surgery. 2010;147:720–8.CrossRefPubMed

14.

Musulén E, Sanz C, Muñoz-Mármol AM, Ariza A. Mismatch repair protein immunohistochemistry: a useful population screening strategy for Lynch syndrome. Hum Pathol. 2014;45:1388–96.CrossRefPubMed

15.

Tajima Y, Kumamoto K, Ito T, Matsuzawa T, Ishiguro T, Kumagai Y, et al. Pit Fall of First Screening of Lynch Syndrome from Medical Records (in Japanese with English abstract). Nihon Gekakeirengo Gakkaishi (Journal of Japanese College of Surgeons). 2013;38:944–9.CrossRef

16.

Urso E, Pucciarelli S, Agostini M, Maretto I, Mescoli C, Bertorelle R, et al. Proximal colon cancer in patients aged 51–60 years of age should be tested for microsatellites instability. A comment on the Revised Bethesda Guidelines. Int J Colorectal Dis. 2008;23:801–6.CrossRefPubMed

17.

Chou CL, Lin JK, Wang HS, Yang SH, Li AF, Chang SC. Microsatellite instability screening should be done for right-sided colon cancer patients less than 60 years of age. Int J Colorectal Dis. 2010;25:47–52.CrossRefPubMed

18.

19.

Giardiello FM, Allen JI, Axilbund JE, Boland CR, Burke CA, Burt RW, et al. Guidelines on genetic evaluation and management of Lynch syndrome: a consensus statement by the US Multi-Society Task Force on colorectal cancer. Gastroenterology. 2014;147:502–26.CrossRefPubMed

20.

Balmaña J, Balaguer F, Cervantes A, Arnold D, ESMO Guidelines Working Group. Familial risk-colorectal cancer: ESMO clinical practice guidelines. Ann Oncol. 2013;24:vi73–80.CrossRefPubMed

21.

National Comprehensive Cancer Network. Lynch syndrome. NCCN Clinical Practice Guidelines in Oncology. Genetic/Familial High-Risk Assessment: colorectal Version 2. 2014. National Comprehensive Cancer Network, 2014.

22.

Sie AS, Mensenkamp AR, Adang EM, Ligtenberg MJ, Hoogerbrugge N. Fourfold increased detection of Lynch syndrome by raising age limit for tumour genetic testing from 50 to 70 years is cost-effective. Ann Oncol. 2014;25:2001–7.CrossRefPubMed

23.

Schofield L, Grieu F, Goldblatt J, Amanuel B, Iacopetta B. A state-wide population-based program for detection of lynch syndrome based upon immunohistochemical and molecular testing of colorectal tumours. Fam Cancer. 2012;11:1–6.CrossRefPubMed

24.

Xicola RM, Llor X, Pons E, Castells A, Alenda C, Piñol V, et al. Performance of different microsatellite marker panels for detection of mismatch repair-deficient colorectal tumors. J Natl Cancer Inst. 2007;99:244–52.CrossRefPubMed

25.

Hatch SB, Lightfoot HM Jr, Garwacki CP, Moore DT, Calvo BF, Woosley JT, et al. Microsatellite instability testing in colorectal carcinoma: choice of markers affects sensitivity of detection of mismatch repair-deficient tumors. Clin Cancer Res. 2005;11:2180–7.CrossRefPubMed

26.

Shia J, Tang LH, Vakiani E, Guillem JG, Stadler ZK, Soslow RA, et al. Immunohistochemistry as first-line screening for detecting colorectal cancer patients at risk for hereditary nonpolyposis colorectal cancer syndrome: a 2-antibody panel may be as predictive as a 4-antibody panel. Am J Surg Pathol. 2009;33:1639–45.CrossRefPubMed

27.

Bartley AN, Luthra R, Saraiya DS, Urbauer DL, Broaddus RR. Identification of cancer patients with Lynch syndrome: clinically significant discordances and problems in tissue-based mismatch repair testing. Cancer Prev Res (Phila). 2012;5:320–7.CrossRef

28.

Rigau V, Sebbagh N, Olschwang S, Paraf F, Mourra N, Parc Y, et al. Microsatellite instability in colorectal carcinoma. The comparison of immunohistochemistry and molecular biology suggests a role for hMSH6 immunostaining. Arch Pathol Lab Med. 2003;127:694–700.PubMed

29.

Lindor NM, Burgart LJ, Leontovich O, Goldberg RM, Cunningham JM, Sargent DJ, et al. Immunohistochemistry versus microsatellite instability testing in phenotyping colorectal tumors. J Clin Oncol. 2002;20:1043–8.CrossRefPubMed

30.

Pino MS, Chung DC. Microsatellite instability in the management of colorectal cancer. Expert Rev Gastroenterol Hepatol. 2011;5:385–99.CrossRefPubMed

31.

Klarskov L, Holck S, Bernstein I, Okkels H, Rambech E, Baldetorp B, et al. Challenges in the identification of MSH6-associated colorectal cancer: rectal location, less typical histology, and a subset with retained mismatch repair function. Am J Surg Pathol. 2011;35:1391–9.CrossRefPubMed

32.

Kastrinos F, Syngal S. Screening patients with colorectal cancer for Lynch syndrome: what are we waiting for? J Clin Oncol. 2012;30:1024–7.CrossRefPubMed

33.

Terui H, Tachikawa T, Kakuta M, Nishimura Y, Yatsuoka T, Yamaguchi K, et al. Molecular and clinical characteristics of MSH6 germline variants detected in colorectal cancer patients. Oncol Rep. 2013;30:2909–16.PubMed

34.

de Wind N, Dekker M, Claij N, Jansen L, van Klink Y, Radman M, et al. HNPCC-like cancer predisposition in mice through simultaneous loss of Msh3 and Msh6 mismatch-repair protein functions. Nat Genet. 1999;23:359–62.CrossRefPubMed

35.

Kang SY, Park CK, Chang DK, Kim JW, Son HJ, Cho YB, et al. Lynch-like syndrome: characterization and comparison with EPCAM deletion carriers. Int J Cancer. 2015;136:1568–78.CrossRefPubMed

36.

Rodríguez-Soler M, Pérez-Carbonell L, Guarinos C, Zapater P, Castillejo A, Barberá VM, et al. Risk of cancer in cases of suspected lynch syndrome without germline mutation. Gastroenterology. 2013;144:926–32.CrossRefPubMed

37.

Yamaguchi T, Furukawa Y, Nakamura Y, Matsubara N, Ishikawa H, Arai M, et al. Comparison of clinical features between suspected familial colorectal cancer type X and Lynch syndrome in Japanese patients with colorectal cancer: a cross-sectional study conducted by the Japanese Society for Cancer of the Colon and Rectum. Jpn J Clin Oncol. 2015;45:153–9.CrossRefPubMed

38.

Thompson BA, Spurdle AB, Plazzer JP, Greenblatt MS, Akagi K, Al-Mulla F, et al. Application of a 5-tiered scheme for standardized classification of 2,360 unique mismatch repair gene variants in the InSiGHT locus-specific database. Nat Genet. 2014;46:107–15.CrossRefPubMedPubMedCentral

39.

Ohsawa T, Sahara T, Muramatsu S, Nishimura Y, Yathuoka T, Tanaka Y, et al. Colorectal cancer susceptibility associated with the hMLH1 V384D variant. Mol Med Rep. 2009;2:887–91.PubMed

Title: Lower prevalence of Lynch syndrome in colorectal cancer patients in a Japanese hospital-based population
Authors: Kensuke Kumamoto
Hideyuki Ishida
Okihide Suzuki
Yusuke Tajima
Noriyasu Chika
Koki Kuwabara
Keiichiro Ishibashi
Katsuharu Saito
Koji Nagata
Hidetaka Eguchi
Junichi Tamaru
Takeo Iwama
Publication date: 01-06-2016
Publisher: Springer Japan
Published in: Surgery Today / Issue 6/2016
Print ISSN: 0941-1291
Electronic ISSN: 1436-2813
DOI: https://doi.org/10.1007/s00595-015-1232-1

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Lower prevalence of Lynch syndrome in colorectal cancer patients in a Japanese hospital-based population

Abstract

Purpose

Methods

Results

Conclusion

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 6/2016

Laparoscopic versus open distal gastrectomy for early gastric cancer in Japan: long-term clinical outcomes of a randomized clinical trial

Long-term results after treatment of the ascending aorta for bicuspid aortic valve patients

Career pathways of board-certified surgeons in Japan

Hybrid video-assisted and limited open (VALO) resection of superior sulcus tumors

Clinical importance of a transcription reverse-transcription concerted (TRC) diagnosis using peritoneal lavage fluids obtained pre- and post-lymphadenectomy from gastric cancer patients

Outcomes of initial surgery in patients with clinical N2 non-small cell lung cancer who met 4 specific criteria