Mismatch repair deficiency in Lynch syndrome-associated colorectal adenomas is more prevalent in older patients.

Tanaka M1,2,3, Nakajima T4, Sugano K5, Yoshida T6, Taniguchi H1, Kanemitsu Y2, Nagino M3, Sekine S1,7.

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Abstract

AIMS:

The aim of this study was to examine the expression of mismatch repair (MMR) proteins in Lynch syndrome (LS)-associated colorectal adenomas and to evaluate their relationship with clinicopathological variables and potential utility in LS screening.

METHODS AND RESULTS:

We performed immunohistochemistry for MLH1, PMS2, MSH2 and MSH6 in 134 adenomas obtained from 26 genetically confirmed LS patients. MMR deficiency, as determined by loss of any MMR protein, was observed in 113 adenomas (84%). All of the MMR-deficient adenomas exhibited homogeneous loss of MMR proteins, which reflected underlying germline mutations. MMR deficiency was more frequent in adenomas obtained from older patients (≥60 year-old; 81/86, 94%), with larger tumor size (>5 mm; 71/73, 97%), and with high-grade dysplasia (50/51, 98%). Multivariate analyses indicated that increased age and larger tumor size were independently associated with MMR deficiency.

CONCLUSIONS:

This study shows that MMR deficiency is significantly associated with increased age, in addition to two previously reported factors-larger size and high-grade dysplasia. When adenomas are analyzed during LS screening, high sensitivity is expected if the adenomas are associated with any of these three factors. This article is protected by copyright. All rights reserved.