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Mismatch repair deficiency in Lynch syndrome‐associated colorectal adenomas is more prevalent in older patients
Author(s) -
Tanaka Masahiro,
Nakajima Takeshi,
Sugano Kokichi,
Yoshida Teruhiko,
Taniguchi Hirokazu,
Kanemitsu Yukihide,
Nagino Masato,
Sekine Shigeki
Publication year - 2016
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.12941
Subject(s) - lynch syndrome , dysplasia , medicine , dna mismatch repair , germline , gastroenterology , germline mutation , adenoma , microsatellite instability , colorectal cancer , oncology , pathology , mutation , cancer , biology , genetics , allele , microsatellite , gene
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 MLH 1, PMS 2, MSH 2 and MSH 6 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 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 (aged ≥60 years; 81 of 86, 94%), with larger tumour size (>5 mm; 71 of 73, 97%) and with high‐grade dysplasia (50 of 51, 98%). Multivariate analyses indicated that increased age and larger tumour size were associated independently with MMR deficiency. Conclusions This study shows that MMR deficiency is associated significantly with increased age, in addition to two previously reported factors–larger size and high‐grade dysplasia. When adenomas are analysed during LS screening, high sensitivity is expected if the adenomas are associated with any of these three factors.