Abstract
Germline mutations in DNA mismatch repair (MMR) genes MLH1, MSH2, MSH6 and PMS2 cause autosomal dominantly inherited Lynch syndrome. Lynch syndrome patients and their families benefit from life-saving intensive cancer surveillance. Approximately one in 30 colorectal cancers arises in the setting of Lynch syndrome. The aim of this study was to assess the detection rate of Lynch syndrome at our institution after introduction of systematic immunohistochemical screening for MMR deficiency in colorectal cancers from 2011 to 2015. Following the recommendations by the Evaluation of Genomic Applications in Practice and Prevention working group all colorectal cancers were immunohistochemically stained for the presence of MMR proteins MLH1, PMS2, MSH2 and MSH6, independent of clinical criteria. In the case of loss of MLH1, the somatic BRAF mutation V600E was assessed with molecular testing and/or immunohistochemistry. Clinical follow-up of potential Lynch syndrome carriers (patients with tumours showing loss of MLH1 expression with absence of BRAFV600E, loss of PMS2, MSH2 or MSH6) was evaluated. Of all patients (n = 486), loss of MMR protein expression was found in 73 (15.0%) tumours. Twenty-eight (6.0%) were classified as potential Lynch syndrome carriers. Of the genetically tested potential Lynch syndrome carriers (10 out of 28 patients), 40% were first diagnosed with Lynch syndrome. Implementation of systematic immunohistochemistry screening for Lynch syndrome showed that 6% of colorectal cancers were potentially Lynch-syndrome related. Tumour board protocols should systematically contain information on MMR status of all colorectal cancers and, in MMR deficient cases, include clear recommendations for genetic counselling for all potential Lynch syndrome patients.
Highlights
Colorectal cancer represents the third most common cancer worldwide and the second leading cause of cancer-related deaths after lung cancer [1]
Lynch syndrome patients and their families benefit from life-saving intensive cancer surveillance
DESIGN: Following the recommendations by the Evaluation of Genomic Applications in Practice and Prevention working group all colorectal cancers were immunohistochemically stained for the presence of mismatch repair (MMR) proteins MLH1, PMS2, MSH2 and MSH6, independent of clinical criteria
Summary
Colorectal cancer represents the third most common cancer worldwide and the second leading cause of cancer-related deaths after lung cancer [1]. Several strategies have been developed to identify patients with Lynch syndrome Since clinical criteria such as the Bethesda Guidelines or the Amsterdam Criteria are difficult to implement in daily clinical practice [2, 3] and studies showed poor sensitivity and/or specificity [4, 5], in 2009 the Evaluation of Genomic Applications in Practice and Prevention (EGAPP) recommended screening all newly diagnosed patients with colorectal cancer for Lynch syndrome [6]. Recent studies pointed out that, universal screening of patients with colorectal cancer is conceptually possible, the implementation of systematic screening is demanding, requiring awareness of the importance of Lynch syndrome screening and close cooperation and effective communication across multiple disciplines [10, 11]
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