TY - JOUR
T1 - Prospective evaluation of molecular screening for Lynch syndrome in patients with endometrial cancer <= 70 years
AU - Leenen, Celine
AU - Lier, Margot
AU - van Doorn, Lena
AU - Leerdam, M
AU - Kooi, SG
AU - de Waard, J
AU - Hoedemaeker, RF (Robert)
AU - van den Ouweland, Ans
AU - Hulspas, Sanne
AU - Dubbink, Erik jan
AU - Kuipers, Ernst
AU - Wagner, Anja
AU - Dinjens, Winand
AU - Steyerberg, Ewout
PY - 2012
Y1 - 2012
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 (INC) 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 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. (C) 2012 Elsevier Inc. All rights reserved.
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 (INC) 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 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. (C) 2012 Elsevier Inc. All rights reserved.
U2 - 10.1016/j.ygyno.2012.01.049
DO - 10.1016/j.ygyno.2012.01.049
M3 - Article
C2 - 22306203
SN - 0090-8258
VL - 125
SP - 414
EP - 420
JO - Gynecologic Oncology
JF - Gynecologic Oncology
IS - 2
ER -
