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.
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.
Authors: Jinru Shia; David S Klimstra; Khedoudja Nafa; Kenneth Offit; Jose G Guillem; Arnold J Markowitz; William L Gerald; Nathan A Ellis Journal: Am J Surg Pathol Date: 2005-01 Impact factor: 6.394
Authors: M A Rodriguez-Bigas; C R Boland; S R Hamilton; D E Henson; J R Jass; P M Khan; H Lynch; M Perucho; T Smyrk; L Sobin; S Srivastava Journal: J Natl Cancer Inst Date: 1997-12-03 Impact factor: 13.506
Authors: S J Winawer; R H Fletcher; L Miller; F Godlee; M H Stolar; C D Mulrow; S H Woolf; S N Glick; T G Ganiats; J H Bond; L Rosen; J G Zapka; S J Olsen; F M Giardiello; J E Sisk; R Van Antwerp; C Brown-Davis; D A Marciniak; R J Mayer Journal: Gastroenterology Date: 1997-02 Impact factor: 22.682
Authors: Fernando S Velayos; Brian A Allen; Peggy G Conrad; James Gum; Sanjay Kakar; Daniel C Chung; Brindusa Truta; Marvin H Sleisenger; Young S Kim; Jonathan P Terdiman Journal: Am J Gastroenterol Date: 2005-05 Impact factor: 10.864
Authors: B Vogelstein; E R Fearon; S R Hamilton; S E Kern; A C Preisinger; M Leppert; Y Nakamura; R White; A M Smits; J L Bos Journal: N Engl J Med Date: 1988-09-01 Impact factor: 91.245
Authors: Thomas F Imperiale; David R Wagner; Ching Y Lin; Gregory N Larkin; James D Rogge; David F Ransohoff Journal: N Engl J Med Date: 2002-06-06 Impact factor: 91.245
Authors: Andrea E De Jong; Hans Morreau; Marjo Van Puijenbroek; Paul H c Eilers; Juul Wijnen; Fokko M Nagengast; Gerrit Griffioen; Annemieke Cats; Fred H Menko; Jan H Kleibeuker; Hans F A Vasen Journal: Gastroenterology Date: 2004-01 Impact factor: 22.682
Authors: Koah Robin Vierkoetter; Laura A T Kagami; Hyeong Jun Ahn; David M Shimizu; Keith Y Terada Journal: Int J Gynecol Cancer Date: 2016-02 Impact factor: 3.437
Authors: Jamal H Carter; Catherine E Cottrell; Samantha N McNulty; Katinka A Vigh-Conrad; Stephen Lamp; Jonathan W Heusel; Eric J Duncavage Journal: Cold Spring Harb Mol Case Stud Date: 2017-11-21
Authors: Stephanie Wong; Ilmars Lidums; Christophe Rosty; Andrew Ruszkiewicz; Susan Parry; Aung Ko Win; Yoko Tomita; Sina Vatandoust; Amanda Townsend; Dainik Patel; Jennifer E Hardingham; David Roder; Eric Smith; Paul Drew; Julie Marker; Wendy Uylaki; Peter Hewett; Daniel L Worthley; Erin Symonds; Graeme P Young; Timothy J Price; Joanne P Young Journal: BMC Gastroenterol Date: 2017-04-19 Impact factor: 3.067