Clinical Outcomes and Microsatellite Instability Testing of Advanced Colorectal Adenomas in Patients under 45
Rao F Watson, Vladimir M Kushnir, Johnathan Goodwin, Elyas Safar, Reena V Chokshi, Nicholas O Davidson, Riad A Azar, Ilke Nalbantoglu. Washington University School of Medicine, St. Louis, MO
Background: Colorectal cancer (CRC) is the second leading cause of death in the United States. Approximately 10% are diagnosed in patients under 50 years old. The rate of CRC in this age group appears to be increasing and is associated with poorer outcome. One of the most common causes of hereditary CRC is Lynch Syndrome (LS). Revised Bethesda criteria (clinical) are used to detect patients with LS and are known to miss approximately 25% of the cases. LS patients are diagnosed with CRC at an average age of 45, in contrast, <2% of normal populations develop adenomas by 40. Advanced colorectal adenomas (ACA) (villous histology, high grade dysplasia, >1 cm adenoma, or >2 adenomas of any size) represent the final stop on the pathway to CRC. However, their natural history in young patients is incompletely defined. The purpose of this study is to determine the natural history and mismatch repair (MMR) protein status of ACAs by immunohistochemistry (IHC) in the absence of a diagnosis of LS and to establish whether these could represent an additional clinical and tissue marker for LS.
Design: Patients aged 18-45y with identified ACAs from 2001-9 were included. Patients with polyposis syndromes, inflammatory bowel disease, CRC, or follow up of < 1 year were excluded. IHC for the DNA mismatch repair proteins MLH1, PMS2, MSH2, and MSH6 were evaluated as a surrogate marker for microsatellite instability (MSI). Cases were deemed MSI if there was concurrent loss of nuclear staining for MLH1/PMS2 and MSH2/MSH6 or individual loss of PMS2 and MSH6.
Results: 76 patients were identified with a mean age of 40.6y, 40.1% were male and 22 (28.9%) African-American. 17 (24.3%) had a first degree relative with CRC, 24 (34.8%) were smokers, and the mean body mass index was 30.7. All adenomas were resected; average size was 12.9 mm. Mean follow up was 3.3 y; 24 (31.6%) had recurrence (mean time to recurrence of 26.4m). No cases of CRC were identified in follow up. IHC was performed on 66 ACAs with tissue available and only one patient showed MSI with loss of PMS2/MLH1 without recurrence at follow up. However, 36 (44.7%) patients met Bethesda criteria for LS.
Conclusions: Patients <45y with ACAs and without LS had an adenoma recurrence rate comparable to patients with LS. MSI testing by IHC was not informative in this patient population. However, the clinical findings suggest that ACA should prompt close follow up and investigation for LS.
Wednesday, March 6, 2013 9:30 AM
Poster Session V # 94, Wednesday Morning