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

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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.

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Acknowledgments

Supported in part by (NIHMS320979) (VMK) and Grants DK-52574, DK-56260 and HL-38180 to (NOD). This work was also supported by funding from the Buehrle Family fund and the Gale Family fund for colorectal cancer research.

Conflict of interests

None.

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Authors and Affiliations

  1. Division of Gastroenterology, Washington University School of Medicine, 660 South Euclid Ave, Campus Box 8124, St Louis, MO, 63110, USA

    Vladimir M. Kushnir, Jonathan Goodwin, Elyas Safar, Reena V. Chokshi, Riad R. Azar & Nicholas O. Davidson

  2. Department of Pathology, Washington University School of Medicine, St Louis, MO, USA

    ILKe Nalbantoglu & Rao Watson

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  1. Vladimir M. Kushnir
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  2. ILKe Nalbantoglu
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Correspondence to Vladimir M. Kushnir.

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Kushnir, V.M., ILKe Nalbantoglu, Watson, R. et al. Advanced Colorectal Adenomas in Patients Under 45 Years of Age Are Mostly Sporadic. Dig Dis Sci 59, 2757–2764 (2014). https://doi.org/10.1007/s10620-014-3245-9

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  • DOI: https://doi.org/10.1007/s10620-014-3245-9

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