Screening HNPCC syndrome in colorectal cancer: are we doing enough?: OP47


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Abstract

Aim:To assess our screening efficiency in the detection of HNPCC in a unselected population operated upon for a colorectal cancer.Method:One thousand and forty patients wereprospectively included between 2004-2009. HNPCC screening included Bethesda criteria, immunochemistry (IHC) for MLH1, MSH2 and MSH6 and microsatellite instability (MSI) using pentaplex markers. Promoter methylation was assessed in tumours with a loss of MLH1 expression. Gene sequencing was offered to patients with abnormal IHC or MSI status.Results:One hundred and two patients (9.8%) had a loss ofprotein on IHC, 98 (9.4%) had MSI. A discordant result was observed in 10 patients leading toproven HNPCC in five patients (50%). Loss of MLH1 (n = 64) was due to apromoter methylation in 43 patients (67.2%). Overall, 62 patients had one abnormal result without methylation and 24 had a genetic sequencing leading to 19 (79.2%) identified germ line mutations. Loss of MSH2 was associated with a mutation in 93% (14/15) of the cases. Among the 62 patients with abnormal results, 23 did not meet the Besthesda criteria (37.1%).Conclusion:Strict use of the Bestheda criteria may lead to loss of patients with HNPCC. IHC and MSI are complementary and should be used in association to avoid missing undiagnosed patients. Loss of MSH2 on IHC is highly associated with a germ line mutation.

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