Advanced Colorectal Adenomas in Patients Under 45 Years of Age Are Mostly Sporadic

Abstract

Background The presence of advanced adenomas in younger individuals is a criterion for Lynch syndrome (LS). However, the utility of screening advanced adenomas for loss of mismatch repair (MMR) protein expression to identify suspected LS remains unclear. Aims Determine the prevalence of MMR defects to understand whether these patients harbor a defined genetic risk for CRC. Methods The study cohort included adult patients ≤45 years of age with advanced adenomas (villous histology, ≥1 cm in diameter, ≥3 polyps of any size) endoscopically removed between 2001 and 2011. Clinical records were reviewed along with detailed pathological review and immunohistochemical MMR analysis. Results A total of 76 (40.1 % male, age 40.6 ± 5.4 years) patients met inclusion and exclusion criteria. Indications for colonoscopy were gastrointestinal (GI) bleeding 39 (51.3 %), CRC in a first-degree relative 17 (22.4 %) and somatic GI symptoms 20 (26.3 %). Index colonoscopy revealed a median of 1 adenoma (range 1–4), mean diameter of 12.9 ±7.1 mm, 40 (52.6 %) with villous histology. The mean follow-up duration was 3.3 ± 2 years. Recurrent adenomas developed in 24 (31.6 %), of which 8 (10.5 %) were advanced adenomas; none of these patients developed CRC. One of 66 (1.5 %) adenomas available for immunohistochemical (IHC) testing revealed loss of MLH1 and PMS2. Conclusions IHC screening of advanced adenomas from patients younger than 45 years of age identified potential LS in one of 64 patients. The low yield of IHC screening in this population suggests that universal IHC screening of advanced adenomas from patients younger than 45 years of age for MMR defects is not an efficient strategy for identifying LS subjects.

Loss of Mismatch Repair Protein Expression in Unselected Endometrial Adenocarcinoma Precursor Lesions

“…However, screening of unselected adenomas has not been shown to be an effective strategy for identifying novel cases of Lynch syndrome. 37,38,41 Similarly, the current study found only 1 patient, less than 1% of patients with EIN, who demonstrated a pattern of MMR deficiency potentially associated with Lynch syndrome. Although loss of MMR protein expression has been observed in premalignant lesions in patients with Lynch syndrome, 7,25–28 it seems to be a relatively infrequent event in an unselected population of patients with EIN.…”

“…36–41 Shia et al 36 suggested that evaluating adenomas with IHC might be productive in a clinically defined subset of patients, such as those with a strong family history of colorectal cancer. However, screening of unselected adenomas has not been shown to be an effective strategy for identifying novel cases of Lynch syndrome.…”

Risk of developing advanced colorectal neoplasia after removing high‐risk adenoma detected at index colonoscopy in young patients: A KASID study

“…Kushnir et al . reported that advanced adenoma developed in 10.5% of young patients (<45 years) after a mean 3.3 years . Yamaji et al .…”

“…As young adults with CRC often have more aggressive tumor characteristics and show different prognosis compared with older adults, advanced adenoma in young patients may have different characteristics and prognosis compared with those in older patients. However, only a few studies have reported the prognosis of young patients after removing advanced adenoma detected at index colonoscopy . Thus, we aimed to investigate the risk of developing advanced colorectal neoplasm in young patients after removing high‐risk adenoma detected at index colonoscopy compared with that in older patients.…”

Update on immunohistochemistry to identify colorectal tumours with deficient DNA mismatch repair function

“…Patients with LS do not typically present with a polyposis; the development of progressive dMMR appears more important in adenoma progression than in initiation. In a study of 66 advanced adenomas (inclusion criteria of adenoma 1 cm, villous architecture, and/or 3 polyps) in 10 Thus, although we do not typically screen adenomas for LS, in patients with a compelling family history in which no other cancer tissue is available, we will perform MMR IHC. In ten studies examining 424 conventional adenomas in LS patients, the overall frequency of abnormal MMR IHC is 75%, ranging from 50 to 90% in individual studies.…”