A S Tjalsma1, A Wagner2, W N M Dinjens3, P C Ewing-Graham3, L S M Alcalá4, M E R de Groot5, K E Hamoen6, A C van Hof7, W Hofhuis8, L N Hofman9, K J Hoogduin10, J Kaijser11, A C F Makkus12, S J J Mol13, G M Plaisier14, K Schelfhout15, H P M Smedts16, R A Smit17, P J Timmers18, P M L H Vencken19, B Visschers20, A A M van der Wurff21, H C van Doorn22. 1. Department of Gynaecologic Oncology, Erasmus MC Cancer Institute, University Medical Centre Rotterdam, the Netherlands. Electronic address: alberttjalsma@gmail.com. 2. Department of Clinical Genetics, Erasmus MC Cancer Institute, University Medical Centre Rotterdam, the Netherlands. 3. Department of Pathology, Erasmus MC Cancer Institute, University Medical Centre Rotterdam, the Netherlands. 4. Department of Pathology, Amphia Hospital Breda, the Netherlands. 5. Department of Gynaecology, Rivas Zorggroep Gorinchem, the Netherlands. 6. Department of Pathology, Maasstad Hospital Rotterdam, the Netherlands. 7. Department of Gynaecology, Van Weel-Bethesda Hospital Dirksland, the Netherlands. 8. Department of Gynaecology, Franciscus Gasthuis Rotterdam, the Netherlands. 9. Department of Gynaecology, Albert Schweitzer Hospital Dordrecht, the Netherlands. 10. Pathan Rotterdam, the Netherlands. 11. Department of Gynaecology, Ikazia Hospital Rotterdam, the Netherlands. 12. PAL Dordrecht, Laboratory for Pathology Dordrecht, the Netherlands. 13. Department of Pathology, Jeroen Bosch Hospital Den Bosch, the Netherlands. 14. Department of Gynaecology, Elisabeth- TweeSteden Hospital Tilburg, the Netherlands. 15. Department of Pathology, Bravis Hospital Roosendaal/Bergen op Zoom, the Netherlands. 16. Department of Gynaecology, Amphia Hospital Breda, the Netherlands. 17. Department of Gynaecology, Jeroen Bosch Hospital Den Bosch, the Netherlands. 18. Department of Gynaecology, Maasstad Hospital Rotterdam, the Netherlands. 19. Department of Gynaecology, Bravis Hospital Roosendaal/ Bergen op Zoom, the Netherlands. 20. Department of Gynaecology, Zorgsaam Zeeuws-Vlaanderen Hospital Terneuzen, the Netherlands. 21. Department of Pathology, Elisabeth- TweeSteden Hospital Tilburg, the Netherlands. 22. Department of Gynaecologic Oncology, Erasmus MC Cancer Institute, University Medical Centre Rotterdam, the Netherlands.
Abstract
OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.