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 |
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| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
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| Language: | English |
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01-03-2021
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| Abstract | 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. |
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| AbstractList | 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. 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. OBJECTIVEIn 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. METHODSFrom 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. RESULTSIn 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. CONCLUSIONCoverage 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. |
| Author | Wagner, A. Schelfhout, K. Tjalsma, A.S. Kaijser, J. Ewing-Graham, P.C. Hoogduin, K.J. de Groot, M.E.R. Makkus, A.C.F. Timmers, P.J. Vencken, P.M.L.H. Mol, S.J.J. van der Wurff, A.A.M. Dinjens, W.N.M. Hamoen, K.E. Hofman, L.N. van Hof, A.C. Hofhuis, W. van Doorn, H.C. Smedts, H.P.M. Plaisier, G.M. Alcalá, L.S.M. Smit, R.A. Visschers, B. |
| Author_xml | – sequence: 1 givenname: A.S. surname: Tjalsma fullname: Tjalsma, A.S. email: alberttjalsma@gmail.com organization: Department of Gynaecologic Oncology, Erasmus MC Cancer Institute, University Medical Centre Rotterdam, the Netherlands – sequence: 2 givenname: A. surname: Wagner fullname: Wagner, A. organization: Department of Clinical Genetics, Erasmus MC Cancer Institute, University Medical Centre Rotterdam, the Netherlands – sequence: 3 givenname: W.N.M. surname: Dinjens fullname: Dinjens, W.N.M. organization: Department of Pathology, Erasmus MC Cancer Institute, University Medical Centre Rotterdam, the Netherlands – sequence: 4 givenname: P.C. surname: Ewing-Graham fullname: Ewing-Graham, P.C. organization: Department of Pathology, Erasmus MC Cancer Institute, University Medical Centre Rotterdam, the Netherlands – sequence: 5 givenname: L.S.M. surname: Alcalá fullname: Alcalá, L.S.M. organization: Department of Pathology, Amphia Hospital Breda, the Netherlands – sequence: 6 givenname: M.E.R. surname: de Groot fullname: de Groot, M.E.R. organization: Department of Gynaecology, Rivas Zorggroep Gorinchem, the Netherlands – sequence: 7 givenname: K.E. surname: Hamoen fullname: Hamoen, K.E. organization: Department of Pathology, Maasstad Hospital Rotterdam, the Netherlands – sequence: 8 givenname: A.C. surname: van Hof fullname: van Hof, A.C. organization: Department of Gynaecology, Van Weel-Bethesda Hospital Dirksland, the Netherlands – sequence: 9 givenname: W. surname: Hofhuis fullname: Hofhuis, W. organization: Department of Gynaecology, Franciscus Gasthuis Rotterdam, the Netherlands – sequence: 10 givenname: L.N. surname: Hofman fullname: Hofman, L.N. organization: Department of Gynaecology, Albert Schweitzer Hospital Dordrecht, the Netherlands – sequence: 11 givenname: K.J. surname: Hoogduin fullname: Hoogduin, K.J. organization: Pathan Rotterdam, the Netherlands – sequence: 12 givenname: J. surname: Kaijser fullname: Kaijser, J. organization: Department of Gynaecology, Ikazia Hospital Rotterdam, the Netherlands – sequence: 13 givenname: A.C.F. surname: Makkus fullname: Makkus, A.C.F. organization: PAL Dordrecht, Laboratory for Pathology Dordrecht, the Netherlands – sequence: 14 givenname: S.J.J. surname: Mol fullname: Mol, S.J.J. organization: Department of Pathology, Jeroen Bosch Hospital Den Bosch, the Netherlands – sequence: 15 givenname: G.M. surname: Plaisier fullname: Plaisier, G.M. organization: Department of Gynaecology, Elisabeth- TweeSteden Hospital Tilburg, the Netherlands – sequence: 16 givenname: K. surname: Schelfhout fullname: Schelfhout, K. organization: Department of Pathology, Bravis Hospital Roosendaal/Bergen op Zoom, the Netherlands – sequence: 17 givenname: H.P.M. surname: Smedts fullname: Smedts, H.P.M. organization: Department of Gynaecology, Amphia Hospital Breda, the Netherlands – sequence: 18 givenname: R.A. surname: Smit fullname: Smit, R.A. organization: Department of Gynaecology, Jeroen Bosch Hospital Den Bosch, the Netherlands – sequence: 19 givenname: P.J. surname: Timmers fullname: Timmers, P.J. organization: Department of Gynaecology, Maasstad Hospital Rotterdam, the Netherlands – sequence: 20 givenname: P.M.L.H. surname: Vencken fullname: Vencken, P.M.L.H. organization: Department of Gynaecology, Bravis Hospital Roosendaal/ Bergen op Zoom, the Netherlands – sequence: 21 givenname: B. surname: Visschers fullname: Visschers, B. organization: Department of Gynaecology, Zorgsaam Zeeuws-Vlaanderen Hospital Terneuzen, the Netherlands – sequence: 22 givenname: A.A.M. surname: van der Wurff fullname: van der Wurff, A.A.M. organization: Department of Pathology, Elisabeth- TweeSteden Hospital Tilburg, the Netherlands – sequence: 23 givenname: H.C. surname: van Doorn fullname: van Doorn, H.C. organization: Department of Gynaecologic Oncology, Erasmus MC Cancer Institute, University Medical Centre Rotterdam, the Netherlands |
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| Issue | 3 |
| Keywords | LLS MSI MMR IHC MMRd LS LSS |
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