Abstract 798: Adenomas in Lynch syndrome: Diagnostically useful

Abstract

Abstract Background: Debate continues as to the usefulness of testing adenomas for loss of mismatch repair (MMR) proteins to identify individuals with suspected Lynch syndrome. Several studies have suggested that it is only worthwhile testing large, proximal adenomas exhibiting high grade dysplasia while others report disappointing “hit rates” even from known mutation carriers. Screening of unselected early-onset adenomas for MMR deficiency has yielded disappointing results. Design: We tested 88 adenomas from 49 proven mutation carriers (23 female and 26 male) from 37 Lynch syndrome families (12 MLH1, 21 MSH2, 3 MSH6 and 1 PMS2) enrolled in the Australasian Colorectal Cancer Family Study which is part of the Colon Collaborative Family Registry (C-CFR). The average age of diagnosis of first polyp studied was 49.1 ± 9.6 years (ranging from 30.3 to 72.0 years). All polyps were tested by immunohistochemistry (IHC) for the four MMR proteins MLH1, MSH2, MSH6 and PMS2. In addition, microsatellite instability testing using a panel of 10 markers (incorporating the standard NCI panel) was performed on 69 adenomas. All polyps were subjected to a standard review by one specialist pathologist (JJ). The majority of adenomas included in the present study were tubular adenomas (n = 61), with 22 tubulovillous adenomas, 1 villous adenoma, and 4 traditional serrated adenomas. Results: Overall, abnormal immunohistochemical results (loss of expression) were noted for 73/88 (82.9%) of the adenomas from MMR gene mutation carriers. In all instances, loss of expression was consistent with the underlying germline mutation. MSI testing was concordant with immunohistochemistry in 66/69 (95.6%) cases. There was no statistical difference in patient ages at the time of polypectomy between MMR deficient and intact adenomas (49.6 ± 9.5 yrs vs. 49.8 ± 11.6 yrs). 15/88 (17.1%) polyps demonstrated normal MMR IHC. Six of these polyps came from four individuals who had other polyps which demonstrated abnormal IHC), whilst the remaining nine adenomas came from nine individuals for whom other adenomas had not been tested. Of these 9 cases, however, three had been diagnosed with Lynch syndrome-spectrum tumours which showed appropriate loss of MMR protein(s) Conclusions: Diagnostic testing of adenomas from patients from Lynch syndrome families is a useful alternative in cases where cancers are unavailable. The overwhelming majority (82.9%) of adenomas from carriers show appropriate loss of MMR proteins and a high level of concordant microsatellite instability. We were unable to demonstrate an association between adenoma grade, size or site and MMR deficiency. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 798.