TY - JOUR
T1 - Prospective evaluation of molecular screening for Lynch syndrome in patients with endometrial cancer ≤ 70 years
AU - Leenen, Celine H.M.
AU - Van Lier, Margot G.F.
AU - Van Doorn, Helena C.
AU - Van Leerdam, Monique E.
AU - Kooi, Sjarlot G.
AU - De Waard, Judith
AU - Hoedemaeker, Robert F.
AU - Van Den Ouweland, Ans M.W.
AU - Hulspas, Sanne M.
AU - Dubbink, Hendrikus J.
AU - Kuipers, Ernst J.
AU - Wagner, Anja
AU - Dinjens, Winand N.M.
AU - Steyerberg, Ewout W.
PY - 2012/5
Y1 - 2012/5
N2 - Objective: Lynch syndrome (LS) is a hereditary syndrome that predisposes to multiple malignancies including endometrial cancer (EC). We aimed to evaluate a diagnostic strategy for LS based on routine analysis of microsatellite instability (MSI) and immunohistochemical (IHC) staining for mismatch repair (MMR) proteins in tumour tissue of all newly diagnosed EC patients ≤ 70 years. Methods: Consecutive EC patients ≤ 70 years were included prospectively in eight Dutch centres. EC specimens were analysed for MSI, IHC of four MMR proteins, MMR gene methylation status and BRAF-mutations. tumours were classified as; 1) likely to be caused by LS, 2) sporadic MSI-H, or 3) microsatellite stable (MSS). Results: Tumour specimens of 179 patients (median age 61 years, IQR 57-66) were analysed. In our study 92% of included patients were over 50 years of age. Eleven EC patients were found likely to have LS (6%; 95% CI 3-11%), including 1 patient suspected of an MLH1, 2 of an MSH2, 6 of an MSH6 and 2 of a PMS2 gene defect. Germline mutation analyses revealed 7 MMR gene germline mutations. Ten patients likely to have LS (92%) were older than 50 years. In addition, 31 sporadic MSI-H tumours with MLH1 promoter hypermethylation (17%; 95% CI 13-24%) were identified. Conclusions: Molecular screening for LS in patients with EC diagnosed ≤ 70 years, leads to identification of a profile likely to have LS in 6% of cases. New screening guidelines for LS are needed, including recommendations for EC patients older than 50 years of age.
AB - Objective: Lynch syndrome (LS) is a hereditary syndrome that predisposes to multiple malignancies including endometrial cancer (EC). We aimed to evaluate a diagnostic strategy for LS based on routine analysis of microsatellite instability (MSI) and immunohistochemical (IHC) staining for mismatch repair (MMR) proteins in tumour tissue of all newly diagnosed EC patients ≤ 70 years. Methods: Consecutive EC patients ≤ 70 years were included prospectively in eight Dutch centres. EC specimens were analysed for MSI, IHC of four MMR proteins, MMR gene methylation status and BRAF-mutations. tumours were classified as; 1) likely to be caused by LS, 2) sporadic MSI-H, or 3) microsatellite stable (MSS). Results: Tumour specimens of 179 patients (median age 61 years, IQR 57-66) were analysed. In our study 92% of included patients were over 50 years of age. Eleven EC patients were found likely to have LS (6%; 95% CI 3-11%), including 1 patient suspected of an MLH1, 2 of an MSH2, 6 of an MSH6 and 2 of a PMS2 gene defect. Germline mutation analyses revealed 7 MMR gene germline mutations. Ten patients likely to have LS (92%) were older than 50 years. In addition, 31 sporadic MSI-H tumours with MLH1 promoter hypermethylation (17%; 95% CI 13-24%) were identified. Conclusions: Molecular screening for LS in patients with EC diagnosed ≤ 70 years, leads to identification of a profile likely to have LS in 6% of cases. New screening guidelines for LS are needed, including recommendations for EC patients older than 50 years of age.
KW - Endometrial cancer
KW - Hereditary cancer
KW - Immunohistochemistry
KW - Lynch syndrome
KW - Microsatellite instability
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U2 - 10.1016/j.ygyno.2012.01.049
DO - 10.1016/j.ygyno.2012.01.049
M3 - Article
C2 - 22306203
AN - SCOPUS:84859566031
SN - 0090-8258
VL - 125
SP - 414
EP - 420
JO - Gynecologic Oncology
JF - Gynecologic Oncology
IS - 2
ER -
