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ISSN (Print): 1573-4048
ISSN (Online): 1875-6581

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Research Article

Lynch Syndrome Identification in Endometrial Cancer Patients: Should Universal Screening be Used for all Histologies?

Author(s): Jessica E. Parker*, Caitlin Mauer, Wenxin Zheng, David S. Miller and Jayanthi S. Lea

Volume 18, Issue 2, 2022

Published on: 02 March, 2021

Article ID: e241221191974 Pages: 7

DOI: 10.2174/1573404817666210302153551

Price: $65

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Abstract

Background: There is an increased proportion of non-endometrioid histologies in Lynch syndrome-associated compared to sporadic endometrial cancer; however, screening recommendations do not differ between type I and type II cancers.

Objective: Our objective was to examine the frequency of Lynch syndrome identified in type I and type II endometrial cancers and their associated characteristics.

Methods: We reviewed patients with type I and type II endometrial cancer who were screened for Lynch Syndrome or referred for genetic testing according to an age and family history-based screening protocol. All patients were seen and treated at a large academic institution affiliated with a county safety-net hospital. Clinical, pathologic, immunohistochemistry, and germline genetic testing results were obtained as well as the choice of genetic screening approach, personal and family history, and compliance with testing were assessed.

Results: 234 women with type I and 29 patients with type II endometrial cancer were identified. Lynch syndrome was diagnosed in a total of eight (3.4%) type I endometrial cancer patients, all identified after age-based tumor screening. In type II endometrial cancer group, three (10.3%) patients had Lynch syndrome. One was referred for testing after abnormal immunohistochemistry screening under age 60. The other two were >60 years old and identified after abnormal immunohistochemistry screening performed on physician’s request.

Conclusion: Age-based screening may not diagnose Lynch Syndrome in women with type II endometrial cancers. Our findings underscore the need for a universal screening approach in patients with type II endometrial cancers, even in a low-resource population.

Keywords: Lynch syndrome, endometrial cancer, genetic testing, screening, safety-net hospital, mismatch repair.

Graphical Abstract

[1]
Aaltonen LA, Salovaara R, Kristo P, et al. Incidence of hereditary nonpolyposis colorectal cancer and the feasibility of molecular screening for the disease. N Engl J Med 1998; 338(21): 1481-7.
[http://dx.doi.org/10.1056/NEJM199805213382101] [PMID: 9593786]
[2]
Resnick KE, Hampel H, Fishel R, Cohn DE. Current and emerging trends in Lynch syndrome identification in women with endometrial cancer. Gynecol Oncol 2009; 114(1): 128-34.
[http://dx.doi.org/10.1016/j.ygyno.2009.03.003] [PMID: 19375789]
[3]
Boland CR, Goel A. Microsatellite instability in colorectal cancer. Gastroenterology 2010; 138: 2073-87.
[http://dx.doi.org/10.1053/j.gastro.2009.12.064]
[4]
Kempers MJ, Kuiper RP, Ockeloen CW, et al. Risk of colorectal and endometrial cancers in EPCAM deletion-positive Lynch syndrome: a cohort study. Lancet Oncol 2011; 12(1): 49-55.
[http://dx.doi.org/10.1016/S1470-2045(10)70265-5] [PMID: 21145788]
[5]
Aarnio M, Sankila R, Pukkala E, et al. Cancer risk in mutation carriers of DNA-mismatch-repair genes. Int J Cancer 1999; 81(2): 214-8.
[http://dx.doi.org/10.1002/(SICI)1097-0215(19990412)81:2<214::AID-IJC8>3.0.CO;2-L] [PMID: 10188721]
[6]
Dunlop MG, Farrington SM, Carothers AD, et al. Cancer risk associated with germline DNA mismatch repair gene mutations. Hum Mol Genet 1997; 6(1): 105-10.
[http://dx.doi.org/10.1093/hmg/6.1.105] [PMID: 9002677]
[7]
Randall LM, Pothuri B, Swisher EM, et al. Multi-disciplinary summit on genetics services for women with gynecologic cancers: A Society of Gynecologic Oncology White Paper. Gynecol Oncol 2017; 146(2): 217-24.
[http://dx.doi.org/10.1016/j.ygyno.2017.06.002] [PMID: 28596016]
[8]
Umar A, Boland CR, Terdiman JP, et al. Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst 2004; 96(4): 261-8.
[http://dx.doi.org/10.1093/jnci/djh034] [PMID: 14970275]
[9]
Vasen HF, Watson P, Mecklin JP, Lynch HT. New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative group on HNPCC. Gastroenterology 1999; 116(6): 1453-6.
[http://dx.doi.org/10.1016/S0016-5085(99)70510-X] [PMID: 10348829]
[10]
National Comprehensive Cancer Network. Genetic/Familial High- Risk Asessment:Colorectal (Version 1.2018) 2018. Available from: https://www.nccn.org/professionals/physician_gls/pdf/genetics_-colon.pdf
[11]
Marquez E, Geng Z, Pass S, et al. Implementation of routine screening for Lynch syndrome in university and safety-net health system settings: successes and challenges. Genet Med 2013; 15(12): 925-32.
[http://dx.doi.org/10.1038/gim.2013.45] [PMID: 23598716]
[12]
Carcangiu ML, Radice P, Casalini P, Bertario L, Merola M, Sala P. Lynch syndrome- related endometrial carcinomas show a high frequency of nonendometrioid types and of high FIGO grade endometrioid types. Int J Surg Pathol 2010; 18(1): 21-6.
[http://dx.doi.org/10.1177/1066896909332117] [PMID: 19443869]
[13]
Broaddus RR, Lynch HT, Chen LM, et al. Pathologic features of endometrial carcinoma associated with HNPCC: a comparison with sporadic endometrial carcinoma. Cancer 2006; 106(1): 87-94.
[http://dx.doi.org/10.1002/cncr.21560] [PMID: 16323174]
[14]
Brinton LA, Felix AS, McMeekin DS, et al. Etiologic heterogeneity in endometrial cancer: evidence from a Gynecologic Oncology Group Trial. Gynecol Oncol 2013; 129(2): 277-84.
[http://dx.doi.org/10.1016/j.ygyno.2013.02.023]
[15]
Ferguson SE, Aronson M, Pollett A, et al. Performance characteristics of screening strategies for Lynch syndrome in unselected women with newly diagnosed endometrial cancer who have undergone universal germline mutation testing. Cancer 2014; 120(24): 3932-9.
[http://dx.doi.org/10.1002/cncr.28933] [PMID: 25081409]
[16]
Kwon JS, Scott JL, Gilks CB, Daniels MS, Sun CC, Lu KH. Testing women with endometrial cancer to detect Lynch syndrome. J Clin Oncol 2011; 29(16): 2247-52.
[http://dx.doi.org/10.1200/JCO.2010.32.9979] [PMID: 21537049]
[17]
Hampel H, Frankel W, Panescu J, et al. Screening for Lynch syndrome (hereditary nonpolyposis colorectal cancer) among endometrial cancer patients. Cancer Res 2006; 66(15): 7810-7. [published addendum appears in Cancer Res 2007;67:9603].
[http://dx.doi.org/10.1158/0008-5472.CAN-06-1114] [PMID: 16885385]
[18]
Moreira L, Balaguer F, Lindor N, et al. Pathologic features of endometrial carcinoma associated with HNPCC: A comparison with sporadic endometrial carcinoma. Cancer 2006; 106(1): 87-94.
[http://dx.doi.org/10.1001/jama.2012.13088]
[19]
Watkins JC, Yang EJ, Muto MG, et al. Universal screening for mismatch-repair deficiency in endometrial cancers to identify patients with Lynch syndrome and Lynch-like syndrome. Int J Gyn Pathol 2017; 36(20): 115-27.
[http://dx.doi.org/10.1097/PGP.0000000000000312]
[20]
Dottino J, Lairson D, Cantor S, et al. A cost-effectiveness analysis of universal testing for Lynch syndrome in endometrial carcinoma. Gynecol Oncol 2017; 147(1): 203.
[http://dx.doi.org/10.1016/j.ygyno.2017.07.041]
[21]
Felix AS, Weissfeld JL, Stone RA, et al. Factors associated with Type I and Type II endometrial cancer. Cancer Causes Control 2010; 21(11): 1851-6.
[http://dx.doi.org/10.1007/s10552-010-9612-8] [PMID: 20628804]
[22]
Cirisano FD Jr, Robboy SJ, Dodge RK, et al. Epidemiologic and surgicopathologic findings of papillary serous and clear cell endometrial cancers when compared to endometrioid carcinoma. Gynecol Oncol 1999; 74(3): 385-94.
[http://dx.doi.org/10.1006/gyno.1999.5505] [PMID: 10479498]
[23]
Bruegl AS, Ring KL, Daniels M, Fellman BM, Urbauer DL, Broaddus RR. Clinical challenges associated with universal screening for Lynch-syndrome associated endometrial cancer. Cancer Prev Res (Phila) 2017; 10(2): 108-15.
[http://dx.doi.org/10.1158/1940-6207.CAPR-16-0219] [PMID: 27965287]
[24]
Armstrong K, Micco E, Carney A, Stopfer J, Putt M. Racial differences in the use of BRCA1/2 testing among women with a family history of breast or ovarian cancer. JAMA 2005; 293(14): 1729-36.
[http://dx.doi.org/10.1001/jama.293.14.1729] [PMID: 15827311]
[25]
Muller C, Lee SM, Barge W, et al. Low referral rate for genetic testing in racially and ethnically diverse patients despite universal colorectal cancer screening. Clin Gastroenterol Hepatol 2018; 16(12): 1911-1918.e2.
[http://dx.doi.org/10.1016/j.cgh.2018.08.038] [PMID: 30130624]

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