Molecular Screening for Lynch Syndrome in Young Patients With Colorectal Adenomas

The frequency of mismatch repair (MMR) deficiency (dMMR) in patients < 50 years with adenomas without a known germline mutation is unknown. Our aim was to define the frequency of dMMRs in adenomas from patients aged < 50 years.

We identified all patients aged 18 to 49 years who had undergone colonoscopy at Memorial Sloan Kettering Cancer Center from 2008 to 2013 and were identified as having tubular, villous, or tubulovillous adenomas on pathology. Patients with a personal history of colorectal cancer, polyposis syndrome, or inflammatory bowel disease before colonoscopy were excluded. Age, demographic data, family history of cancer, personal history of cancer, use of radiation, reason for colonoscopy, and colonoscopy findings were recorded. Polyps were stained using immunohistochemistry for MLH1, MSH2, MSH6, and PMS2 proteins.

A total of 208 patients with 266 polyps were identified. Of the 266 polyps, 259 could be stained. Of the 208 patients, 82 (40%) were men; their mean age was 44 years. The indication for colonoscopy was screening for 120, diagnostic for 75, and therapeutic for 15. Of the 259 examined polyps, 246 (95%) were tubular adenomas and 13 were tubulovillous adenomas (5%). One patient (0.4%) was found to have dMMRs in 1 polyp. This patient was a 42-year-old woman with a history of endometrial cancer who had undergone colonoscopy for hematochezia. A 15-mm transverse tubular adenoma was found that was deficient in MLH1 and PMS2.

Our results indicate that routine screening of polyps in patients aged < 50 years old is not an effective tool for identifying Lynch syndrome carriers.