Underutilization of MSI-analysis in patients with colorectal cancer at high risk for Lynch Syndrome

M.G.F. van Lier1, J.H.W. de Wilt2, J.J.M.F. Wagemakers3, W.N.M. Dinjens4, R.A.M. Damhuis3, E.J. Kuipers1, M.E. van Leerdam1
Department of Gastroenterology and Hepatology1, Department of Surgery2 and Department of Pathology4, Erasmus University Medical Center, Rotterdam; Comprehensive Cancer Center Rotterdam3

Background: Lynch Syndrome (LS) is responsible for approximately 3-5% of all colorectal carcinomas (CRC). Microsatellite instability (MSI) is the molecular hallmark of LS. In 2004 the revised Bethesda Guidelines were published to improve the efficiency of recognizing LS by identifying LS related malignancies that should be analyzed for MSI. The aim of this study was to evaluate whether MSI-analysis was performed in CRC patients at high risk for LS according to the Bethesda Guidelines in the Southwestern part of the Netherlands.

Methods: All patients diagnosed with invasive CRC in 11 Dutch hospitals between January 2005 and January 2007 were selected from the regional ComprehensiveCancer Center. Data concerning all MSI-analyses between January 2005 and August 2007 were available. Patients were included if they met any of the following criteria derived from the Bethesda Guidelines: (1) patients diagnosed with CRC < 50 years, (2) patients diagnosed with a second LS-associated tumor prior to the diagnosis of CRC in 2005/2006, and (3) patients < 60 years with CRC displaying mucinous or signet-ring differentiation or medullary growth pattern. Patients were excluded when they had previously been identified as LS mutation carrier. MSI performance rates were analyzed using chi square statistics. Family history and presence of tumor-infiltrating lymphocytes or Crohn's-like lymphocytic reaction in the tumor were not taken into account since these data were missing.

Results: Of the 1905 patients diagnosed with CRC, 169 (8%) met at least one of the 3 inclusion criteria. There were no known LS mutation carriers. MSI-analysis had been performed in 23 (13,6%) of the 169 tumors. MSI-analysis was performed in 18 (22,5%) of the 80 included patients < 50 years of age, and in 4 (6%) of the 70 patients with a second LS-related tumor. Of the 41 patients < 60 years with high-risk pathology markers, 3 (7%) were referred for MSI-analysis. In patients with CRC < 50 years MSI-analysis was significantly more often performed than in patients fulfilling one of the other 2 inclusion criteria (p < 0,01). Gender and tumor localization did not influence MSI-performance in our selected cases.

Conclusions: Despite multidisciplinary approach of oncology and easy access to a tertiary referral center and clinical genetics facilities, there is marked underutilization of MSI-analysis in patients at high risk for Lynch Syndrome. As a result Lynch Syndrome might be under-diagnosed in patients with CRC and their relatives.