Evaluation of a nationwide Dutch guideline to detect Lynch syndrome in patients with endometrial cancer

In the Netherlands a nationwide guideline was introduced in 2016, which recommended routine Lynch syndrome screening (LSS) for all women with endometrial cancer (EC) <70 years of age. LSS consists of immunohistochemical (IHC) staining for loss of mismatch repair (MMR) protein expression, suppleme...

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Published in:	Gynecologic oncology Vol. 160; no. 3; pp. 771 - 776
Main Authors:	Tjalsma, A.S., Wagner, A., Dinjens, W.N.M., Ewing-Graham, P.C., Alcalá, L.S.M., de Groot, M.E.R., Hamoen, K.E., van Hof, A.C., Hofhuis, W., Hofman, L.N., Hoogduin, K.J., Kaijser, J., Makkus, A.C.F., Mol, S.J.J., Plaisier, G.M., Schelfhout, K., Smedts, H.P.M., Smit, R.A., Timmers, P.J., Vencken, P.M.L.H., Visschers, B., van der Wurff, A.A.M., van Doorn, H.C.
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 01-03-2021
Subjects:	LLS MSI MMR IHC MMRd LS LSS
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Summary:	In the Netherlands a nationwide guideline was introduced in 2016, which recommended routine Lynch syndrome screening (LSS) for all women with endometrial cancer (EC) <70 years of age. LSS consists of immunohistochemical (IHC) staining for loss of mismatch repair (MMR) protein expression, supplemented with MLH1 methylation analysis if indicated. Test results are evaluated by the treating gynaecologist, who refers eligible patients to a clinical geneticist. We evaluated the implementation of this guideline. From the nation-wide pathology database we selected all women diagnosed with EC < 70 years of age, treated from 1.6.2016–1.6.2017 in 14 hospitals. We collected data on the results of LSS and follow up of cases with suspected LS. In 183 out of 204 tumours (90%) LSS was performed. In 41 cases (22%) MMR protein expression was lost, in 25 cases due to hypermethylation of the MLH1 promotor. One patient was known with a pathogenic MLH1 variant. The option of genetic counselling was discussed with 12 of the 15 remaining patients, of whom three declined. After counselling by the genetic counsellor nine patients underwent germline testing. In two no pathogenic germline variant was detected, two were diagnosed with a pathogenic PMS2 variant, and five with a pathogenic MSH6 variant, in concordance with the IHC profiles. Coverage of LSS was high (90%), though referral for genetic counselling could be improved. Gynaecologists ought to be aware of the benefits and possible drawbacks of knowing mutational status, and require training in discussing this with their patients. •Implementation of Lynch syndrome screening in endometrial cancer can be improved.•Gynaecologists ought to be aware of Lynch syndrome screening in endometrial cancer and might require additional training.•Quality assurance protocols should be implemented to ensure adherence to Lynch syndrome screening in endometrial cancer.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0090-8258 1095-6859
DOI:	10.1016/j.ygyno.2020.12.028