TY - JOUR
T1 - Yield of routine molecular analyses in colorectal cancer patients ≤ 70 years to detect underlying lynch syndrome
AU - Van Lier, Margot G.F.
AU - Leenen, Celine H.M.
AU - Wagner, Anja
AU - Ramsoekh, Dewkoemar
AU - Dubbink, Hendrikus J.
AU - Van Den Ouweland, Ans M.W.
AU - Westenend, Pieter J.
AU - De Graaf, Eelco J.R.
AU - Wolters, Leonieke M.M.
AU - Vrijland, Wietske W.
AU - Kuipers, Ernst J.
AU - Van Leerdam, Monique E.
AU - Steyerberg, Ewout W.
AU - Dinjens, Winand N.M.
AU - Van Tilburg, G.
AU - Hulspas, S.
AU - Lange, J. F.
AU - Hoedemaeker, R. F.
AU - Bode, W. A.
AU - Van Dam, J. H.
AU - Wismans, P. J.
AU - Den Toom, R.
AU - Van De Weijgert, E. J.H.M.
AU - Van Tilburg, A. J.P.
AU - Lont, H. E.
AU - Van't Hoff, B. W.M.
AU - Oostenbroek, R. J.
AU - Logeman, F.
AU - Van Baalen, O.
AU - Van Den Ingh, H. F.G.M.
AU - Van Der Harst, E.
AU - Kubben, F. J.G.M.
AU - Weidema, W. F.
AU - Ouwendijk, R. J.Th
AU - Van Rijssel, R. H.
AU - Eddes, E. H.
AU - Ter Borg, F.
PY - 2012/4
Y1 - 2012/4
N2 - Although early detection of Lynch syndrome (LS) is important, a considerable proportion of patients with LS remains unrecognized. We aimed to study the yield of LS detection by routine molecular analyses in colorectal cancer (CRC) patients until 70 years of age. We prospectively included consecutive CRC patients ≤ 70 years. Tumour specimens were analysed for microsatellite instability (MSI), immunohistochemical mismatch-repair protein expression and MLH1-promoter methylation. Tumours were classified as either: (a) likely caused by LS; (b) sporadic microsatellite-unstable (MSI-H); or (c) microsatellite-stable (MSS). Predictors of LS were determined by multivariable logistic regression. A total of 1117 CRC patients (57% males, median age 61 years) were included. Fifty patients (4.5%, 95% CI 3.4-5.9) were likely to have LS, and 71 had a sporadic MSI-H tumour (6.4%, 95% CI 5.1-8.0). Thirty-five patients likely to have LS (70%) were aged > 50 years. A molecular profile compatible with LS was detected in 10% (15/144) of patients aged ≤ 50, in 4% (15/377) of those aged 51-60 and in 3% (20/596) of patients > 61 years. Compared to MSS cases, patients likely to have LS were significantly younger (OR 3.9, 95% CI 1.7-8.7) and more often had right-sided CRCs (OR 14, 95% CI 6.0-34). In conclusion, molecular screening for LS in CRC patients ≤ 70 years leads to identification of a molecular profile compatible with LS in 4.5% of patients, with most of them not fulfilling the age criterion (≤ 50 years) routinely used for LS assessment. Routine use of MSI testing may be considered in CRC patients up to the age of 70 years, with a central role for the pathologist in the selection of patients.
AB - Although early detection of Lynch syndrome (LS) is important, a considerable proportion of patients with LS remains unrecognized. We aimed to study the yield of LS detection by routine molecular analyses in colorectal cancer (CRC) patients until 70 years of age. We prospectively included consecutive CRC patients ≤ 70 years. Tumour specimens were analysed for microsatellite instability (MSI), immunohistochemical mismatch-repair protein expression and MLH1-promoter methylation. Tumours were classified as either: (a) likely caused by LS; (b) sporadic microsatellite-unstable (MSI-H); or (c) microsatellite-stable (MSS). Predictors of LS were determined by multivariable logistic regression. A total of 1117 CRC patients (57% males, median age 61 years) were included. Fifty patients (4.5%, 95% CI 3.4-5.9) were likely to have LS, and 71 had a sporadic MSI-H tumour (6.4%, 95% CI 5.1-8.0). Thirty-five patients likely to have LS (70%) were aged > 50 years. A molecular profile compatible with LS was detected in 10% (15/144) of patients aged ≤ 50, in 4% (15/377) of those aged 51-60 and in 3% (20/596) of patients > 61 years. Compared to MSS cases, patients likely to have LS were significantly younger (OR 3.9, 95% CI 1.7-8.7) and more often had right-sided CRCs (OR 14, 95% CI 6.0-34). In conclusion, molecular screening for LS in CRC patients ≤ 70 years leads to identification of a molecular profile compatible with LS in 4.5% of patients, with most of them not fulfilling the age criterion (≤ 50 years) routinely used for LS assessment. Routine use of MSI testing may be considered in CRC patients up to the age of 70 years, with a central role for the pathologist in the selection of patients.
KW - Colorectal cancer
KW - Immunohistochemistry
KW - Lynch syndrome
KW - Microsatellite instability
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U2 - 10.1002/path.3963
DO - 10.1002/path.3963
M3 - Article
C2 - 22081473
AN - SCOPUS:84857993554
SN - 0022-3417
VL - 226
SP - 764
EP - 774
JO - Journal of Pathology
JF - Journal of Pathology
IS - 5
ER -
