Diagnosis of Lynch syndrome before colorectal resection: does it matter?

Abstract

Lynch syndrome (LS), also known as hereditary nonpolyposis colorectal cancer (HNPCC), is an autosomal dominant genetic condition which predisposes patients to several different types of cancer, most notably colorectal cancer [1]. LS can be implicated in up to 5 % of colorectal cancers (CRC), making it the most common form of hereditary CRC [2]. However, in patients with early-onset CRC this number can be up to 17 % [3]. There has been an increased focus on early-onset CRC in general due to recently demonstrated rising CRC incidence rates in this group, although the underlying pathogenic factors are not completely understood [4]. Timing of LS diagnosis in suspected patients is critical, as early identification can facilitate management decisions regarding surgical intervention, colonoscopic surveillance and screening for extracolonic cancers. In addition, expedited germline genetic testing can be offered to at-risk family members.Recent guidelines suggest that all newly diagnosed CRCs, regardless of patient age, can be considered for evaluation for mismatch repair deficiency by microsatellite instability (MSI) and/or immunohistochemistry (IHC) testing for mismatch repair proteins [5]. Germline genetic testing can follow in order to confirm LS and assess for specific underlying mutations. When surgery is indicated, the aforementioned testing should ideally occur preoperatively so that results can assist planning and decision making in the operating room [5]. Due to high rates of metachronous CRC in LS patients undergoing partial colon resections (16 % at 10 years, 41 % at 20 years and 62 % at 30 years), even in those undergoing colonoscopic surveillance, colectomy with ileorectal anastomosis is recommended [5,6]. Studies have demonstrated the rate of metachronous lesions to drop significantly (postoperative risk is 0-3.4 %) when the recommended surgical intervention was performed [6,7]. Given this expanding appreciation for the role that genetic analysis may play in CRC surgical and medical management, the expectations would be for a rise in genetic evaluation, unfortunately the reality seems far from it.A recent study utilizing CDC comparative effectiveness research data conducted by our group evaluated the frequency of MSI and IHC testing in early-onset CRC patients and availability of testing results preoperatively [8]. The study, which was the first population-based study in the USA to evaluate LS screening practices, took place in Louisiana, which was recently demonstrated to have one of the highest incidence rates of CRC in the USA and very high rates of early-onset CRC, particularly in certain regions [9]. Data collected from the Louisiana Tumor Registry totaling 274 patients statewide B50 years of age and diagnosed with CRC in 2011 were analyzed. They found that in this young, high-risk population in which LS screening rates would be expected to be the highest, MSI and/or IHC testing was performed in only 23 % of patients with abnormalities found in 21.7 % of cases. Additionally, of those with abnormal IHC...