Universal Testing in Endometrial Cancer in Sweden

Overview

Journal Hered Cancer Clin Pract

Publisher Biomed Central

Specialty Oncology

Date 2024 Aug 22

PMID 39175077

Authors

Emil Andersson

Anne Keranen

Kristina Lagerstedt-Robinson

Sam Ghazi

Annika Lindblom

Emma Tham

Miriam Mints

Affiliations

Soon will be listed here.

Abstract

Background: The aim of the study was to test a universal screening strategy on endometrial cancer to evaluate its effectiveness to find Lynch Syndrome (LS) cases to two established clinical criteria: Amsterdam II criteria, and the revised Bethesda criteria to select cases for prescreening with immunohistochemistry (IHC). Cases were subsequently screened for germline disease causing variants regarding the DNA mismatch repair (MMR) genes.

Methods: IHC was performed on 221 endometrial cancer (EC) cases, using antibodies against the DNA mismatch repair proteins MLH1, PMS2, MSH2, and MSH6. MMR loss was found in 54 cases, and gene mutation screening was undertaken in 52 of those.

Results: In this set of patients, the use of Amsterdam II criteria detected two (0.9%), the Bethesda criteria two (0.9%), and universal testing five (2.3%) cases of LS. The combination of universal testing and family history criteria resulted in detection of five patients (2.3%) with LS.

Conclusions: Based on our results and other similar studies to date we propose a screening protocol for LS on EC tumors with prescreening using IHC for the four MMR proteins on all new EC cases diagnosed before 70 years of age, followed by mutation screening of all tumors with loss of MSH2 and/or MSH6 or only PMS2, plus consideration for mutation screening of all LS genes in cases fulfilling the clinical Amsterdam II criteria regardless of MMR status on IHC.

References

Goodfellow P, Billingsley C, Lankes H, Ali S, Cohn D, Broaddus R . Combined Microsatellite Instability, MLH1 Methylation Analysis, and Immunohistochemistry for Lynch Syndrome Screening in Endometrial Cancers From GOG210: An NRG Oncology and Gynecologic Oncology Group Study. J Clin Oncol. 2015; 33(36):4301-8. PMC: 4678181. DOI: 10.1200/JCO.2015.63.9518. View

Kwon J, Scott J, Gilks C, Daniels M, Sun C, Lu K . Testing women with endometrial cancer to detect Lynch syndrome. J Clin Oncol. 2011; 29(16):2247-52. PMC: 4874206. DOI: 10.1200/JCO.2010.32.9979. View

Singh S, Resnick K . Lynch Syndrome and Endometrial Cancer. South Med J. 2017; 110(4):265-269. DOI: 10.14423/SMJ.0000000000000633. View

Shia J, Tang L, Vakiani E, Guillem J, Stadler Z, Soslow R . 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(11):1639-45. DOI: 10.1097/PAS.0b013e3181b15aa2. View

Adar T, Rodgers L, Shannon K, Yoshida M, Ma T, Mattia A . Universal screening of both endometrial and colon cancers increases the detection of Lynch syndrome. Cancer. 2018; 124(15):3145-3153. DOI: 10.1002/cncr.31534. View

Egoavil C, Alenda C, Castillejo A, Paya A, Peiro G, Sanchez-Heras A . Prevalence of Lynch syndrome among patients with newly diagnosed endometrial cancers. PLoS One. 2013; 8(11):e79737. PMC: 3820559. DOI: 10.1371/journal.pone.0079737. View

You J, Buhard O, Ligtenberg M, Kets C, Niessen R, Hofstra R . Tumours with loss of MSH6 expression are MSI-H when screened with a pentaplex of five mononucleotide repeats. Br J Cancer. 2010; 103(12):1840-5. PMC: 3008611. DOI: 10.1038/sj.bjc.6605988. View

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J . Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015; 17(5):405-24. PMC: 4544753. DOI: 10.1038/gim.2015.30. View

Leclerc J, Vermaut C, Buisine M . Diagnosis of Lynch Syndrome and Strategies to Distinguish Lynch-Related Tumors from Sporadic MSI/dMMR Tumors. Cancers (Basel). 2021; 13(3). PMC: 7865821. DOI: 10.3390/cancers13030467. View

10.

Tzortzatos G, Wersall O, Gemzell Danielsson K, Lindblom A, Tham E, Mints M . Familial cancer among consecutive uterine cancer patients in Sweden. Hered Cancer Clin Pract. 2014; 12(1):14. PMC: 4029977. DOI: 10.1186/1897-4287-12-14. View

11.

Sjursen W, Haukanes B, Grindedal E, Aarset H, Stormorken A, Engebretsen L . Current clinical criteria for Lynch syndrome are not sensitive enough to identify MSH6 mutation carriers. J Med Genet. 2010; 47(9):579-85. PMC: 2976029. DOI: 10.1136/jmg.2010.077677. View

12.

Park J, Vasen H, Park Y, Park K, Peltomaki P, de Leon M . Suspected HNPCC and Amsterdam criteria II: evaluation of mutation detection rate, an international collaborative study. Int J Colorectal Dis. 2002; 17(2):109-14. DOI: 10.1007/s003840100348. View

13.

Goodfellow P, Buttin B, Herzog T, Rader J, Gibb R, Swisher E . Prevalence of defective DNA mismatch repair and MSH6 mutation in an unselected series of endometrial cancers. Proc Natl Acad Sci U S A. 2003; 100(10):5908-13. PMC: 156300. DOI: 10.1073/pnas.1030231100. View

14.

Ryan N, Davison N, Payne K, Cole A, Evans D, Crosbie E . A Micro-Costing Study of Screening for Lynch Syndrome-Associated Pathogenic Variants in an Unselected Endometrial Cancer Population: Cheap as NGS Chips?. Front Oncol. 2019; 9:61. PMC: 6399107. DOI: 10.3389/fonc.2019.00061. View

15.

Ryan N, McMahon R, Tobi S, Snowsill T, Esquibel S, Wallace A . The proportion of endometrial tumours associated with Lynch syndrome (PETALS): A prospective cross-sectional study. PLoS Med. 2020; 17(9):e1003263. PMC: 7497985. DOI: 10.1371/journal.pmed.1003263. View

16.

Shia J . Immunohistochemistry versus microsatellite instability testing for screening colorectal cancer patients at risk for hereditary nonpolyposis colorectal cancer syndrome. Part I. The utility of immunohistochemistry. J Mol Diagn. 2008; 10(4):293-300. PMC: 2438196. DOI: 10.2353/jmoldx.2008.080031. View

17.

Ryan N, Glaire M, Blake D, Cabrera-Dandy M, Evans D, Crosbie E . The proportion of endometrial cancers associated with Lynch syndrome: a systematic review of the literature and meta-analysis. Genet Med. 2019; 21(10):2167-2180. PMC: 8076013. DOI: 10.1038/s41436-019-0536-8. View

18.

Mills A, Liou S, Ford J, Berek J, Pai R, Longacre T . Lynch syndrome screening should be considered for all patients with newly diagnosed endometrial cancer. Am J Surg Pathol. 2014; 38(11):1501-9. PMC: 4361228. DOI: 10.1097/PAS.0000000000000321. View

19.

Umar A, Boland C, Terdiman J, Syngal S, de la Chapelle A, Ruschoff J . Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst. 2004; 96(4):261-8. PMC: 2933058. DOI: 10.1093/jnci/djh034. View

20.

Hampel H, Frankel W, Panescu J, Lockman J, Sotamaa K, Fix D . Screening for Lynch syndrome (hereditary nonpolyposis colorectal cancer) among endometrial cancer patients. Cancer Res. 2006; 66(15):7810-7. DOI: 10.1158/0008-5472.CAN-06-1114. View