Population-based screening for Lynch syndrome in Western Australia

Lyn Schofield, F. Grieu, Benhur Amanuel, A.C. Carrello, Dominic Spagnolo, C. Kiraly, Nicholas Pachter, Jack Goldblatt, Cameron Platell, M. Levitt, C.J.R. Stewart, P.R. Salama, Hooi Ee, S. Raftopoulous, P. Katris, T.J. Threlfall, E. Edkins, Marina Wallace, Barry Iacopetta

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    Abstract

    We showed earlier that routine screening for microsatellite instability (MSI) and loss of mismatch repair (MMR) protein expression in colorectal cancer (CRC) led to the identification of previously unrecognized cases of Lynch syndrome (LS). We report here the results of screening for LS in Western Australia (WA) during 1994–2012. Immunohistochemistry (IHC) for loss of MMR protein expression was performed in routine pathology laboratories, while MSI was detected in a reference molecular pathology laboratory. Information on germline mutations in MMR genes was obtained from the state's single familial cancer registry. Prior to the introduction of routine laboratory-based screening, an average of 2–3 cases of LS were diagnosed each year amongst WA CRC patients. Following the implementation of IHC and/or MSI screening for all younger (<60 years) CRC patients, this has increased to an average of 8 LS cases diagnosed annually. Based on our experience in WA, we propose three key elements for successful population-based screening of LS. First, for all younger CRC patients, reflex IHC testing should be carried out in accredited pathology services with ongoing quality control. Second, a state- or region-wide reference laboratory for MSI testing should be established to confirm abnormal or suspicious IHC test results and to exclude sporadic cases by carrying out BRAF mutation or MLH1 methylation testing. Finally, a state or regional LS coordinator is essential to ensure that all appropriate cases identified by laboratory testing are referred to and attend a Familial Cancer Clinic for follow-up and germline testing.
    Original languageEnglish
    Pages (from-to)1085-1091
    JournalInternational Journal of Cancer
    Volume135
    Issue number5
    Early online date24 Feb 2014
    DOIs
    Publication statusPublished - 1 Sep 2014

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    Hereditary Nonpolyposis Colorectal Neoplasms
    Western Australia
    Microsatellite Instability
    DNA Mismatch Repair
    Colorectal Neoplasms
    Immunohistochemistry
    Population
    Pathology
    Molecular Pathology
    Germ-Line Mutation
    Quality Control
    Methylation
    Reflex
    Registries
    Neoplasms
    Proteins
    Mutation
    Genes

    Cite this

    Schofield, L., Grieu, F., Amanuel, B., Carrello, A. C., Spagnolo, D., Kiraly, C., ... Iacopetta, B. (2014). Population-based screening for Lynch syndrome in Western Australia. International Journal of Cancer, 135(5), 1085-1091. https://doi.org/10.1002/ijc.28744
    Schofield, Lyn ; Grieu, F. ; Amanuel, Benhur ; Carrello, A.C. ; Spagnolo, Dominic ; Kiraly, C. ; Pachter, Nicholas ; Goldblatt, Jack ; Platell, Cameron ; Levitt, M. ; Stewart, C.J.R. ; Salama, P.R. ; Ee, Hooi ; Raftopoulous, S. ; Katris, P. ; Threlfall, T.J. ; Edkins, E. ; Wallace, Marina ; Iacopetta, Barry. / Population-based screening for Lynch syndrome in Western Australia. In: International Journal of Cancer. 2014 ; Vol. 135, No. 5. pp. 1085-1091.
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    abstract = "We showed earlier that routine screening for microsatellite instability (MSI) and loss of mismatch repair (MMR) protein expression in colorectal cancer (CRC) led to the identification of previously unrecognized cases of Lynch syndrome (LS). We report here the results of screening for LS in Western Australia (WA) during 1994–2012. Immunohistochemistry (IHC) for loss of MMR protein expression was performed in routine pathology laboratories, while MSI was detected in a reference molecular pathology laboratory. Information on germline mutations in MMR genes was obtained from the state's single familial cancer registry. Prior to the introduction of routine laboratory-based screening, an average of 2–3 cases of LS were diagnosed each year amongst WA CRC patients. Following the implementation of IHC and/or MSI screening for all younger (<60 years) CRC patients, this has increased to an average of 8 LS cases diagnosed annually. Based on our experience in WA, we propose three key elements for successful population-based screening of LS. First, for all younger CRC patients, reflex IHC testing should be carried out in accredited pathology services with ongoing quality control. Second, a state- or region-wide reference laboratory for MSI testing should be established to confirm abnormal or suspicious IHC test results and to exclude sporadic cases by carrying out BRAF mutation or MLH1 methylation testing. Finally, a state or regional LS coordinator is essential to ensure that all appropriate cases identified by laboratory testing are referred to and attend a Familial Cancer Clinic for follow-up and germline testing.",
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    Schofield, L, Grieu, F, Amanuel, B, Carrello, AC, Spagnolo, D, Kiraly, C, Pachter, N, Goldblatt, J, Platell, C, Levitt, M, Stewart, CJR, Salama, PR, Ee, H, Raftopoulous, S, Katris, P, Threlfall, TJ, Edkins, E, Wallace, M & Iacopetta, B 2014, 'Population-based screening for Lynch syndrome in Western Australia' International Journal of Cancer, vol. 135, no. 5, pp. 1085-1091. https://doi.org/10.1002/ijc.28744

    Population-based screening for Lynch syndrome in Western Australia. / Schofield, Lyn; Grieu, F.; Amanuel, Benhur; Carrello, A.C.; Spagnolo, Dominic; Kiraly, C.; Pachter, Nicholas; Goldblatt, Jack; Platell, Cameron; Levitt, M.; Stewart, C.J.R.; Salama, P.R.; Ee, Hooi; Raftopoulous, S.; Katris, P.; Threlfall, T.J.; Edkins, E.; Wallace, Marina; Iacopetta, Barry.

    In: International Journal of Cancer, Vol. 135, No. 5, 01.09.2014, p. 1085-1091.

    Research output: Contribution to journalArticle

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    AU - Grieu, F.

    AU - Amanuel, Benhur

    AU - Carrello, A.C.

    AU - Spagnolo, Dominic

    AU - Kiraly, C.

    AU - Pachter, Nicholas

    AU - Goldblatt, Jack

    AU - Platell, Cameron

    AU - Levitt, M.

    AU - Stewart, C.J.R.

    AU - Salama, P.R.

    AU - Ee, Hooi

    AU - Raftopoulous, S.

    AU - Katris, P.

    AU - Threlfall, T.J.

    AU - Edkins, E.

    AU - Wallace, Marina

    AU - Iacopetta, Barry

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    N2 - We showed earlier that routine screening for microsatellite instability (MSI) and loss of mismatch repair (MMR) protein expression in colorectal cancer (CRC) led to the identification of previously unrecognized cases of Lynch syndrome (LS). We report here the results of screening for LS in Western Australia (WA) during 1994–2012. Immunohistochemistry (IHC) for loss of MMR protein expression was performed in routine pathology laboratories, while MSI was detected in a reference molecular pathology laboratory. Information on germline mutations in MMR genes was obtained from the state's single familial cancer registry. Prior to the introduction of routine laboratory-based screening, an average of 2–3 cases of LS were diagnosed each year amongst WA CRC patients. Following the implementation of IHC and/or MSI screening for all younger (<60 years) CRC patients, this has increased to an average of 8 LS cases diagnosed annually. Based on our experience in WA, we propose three key elements for successful population-based screening of LS. First, for all younger CRC patients, reflex IHC testing should be carried out in accredited pathology services with ongoing quality control. Second, a state- or region-wide reference laboratory for MSI testing should be established to confirm abnormal or suspicious IHC test results and to exclude sporadic cases by carrying out BRAF mutation or MLH1 methylation testing. Finally, a state or regional LS coordinator is essential to ensure that all appropriate cases identified by laboratory testing are referred to and attend a Familial Cancer Clinic for follow-up and germline testing.

    AB - We showed earlier that routine screening for microsatellite instability (MSI) and loss of mismatch repair (MMR) protein expression in colorectal cancer (CRC) led to the identification of previously unrecognized cases of Lynch syndrome (LS). We report here the results of screening for LS in Western Australia (WA) during 1994–2012. Immunohistochemistry (IHC) for loss of MMR protein expression was performed in routine pathology laboratories, while MSI was detected in a reference molecular pathology laboratory. Information on germline mutations in MMR genes was obtained from the state's single familial cancer registry. Prior to the introduction of routine laboratory-based screening, an average of 2–3 cases of LS were diagnosed each year amongst WA CRC patients. Following the implementation of IHC and/or MSI screening for all younger (<60 years) CRC patients, this has increased to an average of 8 LS cases diagnosed annually. Based on our experience in WA, we propose three key elements for successful population-based screening of LS. First, for all younger CRC patients, reflex IHC testing should be carried out in accredited pathology services with ongoing quality control. Second, a state- or region-wide reference laboratory for MSI testing should be established to confirm abnormal or suspicious IHC test results and to exclude sporadic cases by carrying out BRAF mutation or MLH1 methylation testing. Finally, a state or regional LS coordinator is essential to ensure that all appropriate cases identified by laboratory testing are referred to and attend a Familial Cancer Clinic for follow-up and germline testing.

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    Schofield L, Grieu F, Amanuel B, Carrello AC, Spagnolo D, Kiraly C et al. Population-based screening for Lynch syndrome in Western Australia. International Journal of Cancer. 2014 Sep 1;135(5):1085-1091. https://doi.org/10.1002/ijc.28744