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

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. 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 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. 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.

Tanaka M ，Nakajima T ，Sugano K ，Yoshida T ，Taniguchi H ，Kanemitsu Y ，Nagino M ，Sekine S ... -  《-》

Lynch Syndrome in Thai Endometrial Cancer Patients.

Manchana T ，Ariyasriwatana C ，Triratanachat S ，Phowthongkum P ... -  《-》

Functional Repair Assay for the Diagnosis of Constitutional Mismatch Repair Deficiency From Non-Neoplastic Tissue.

Shuen AY ，Lanni S ，Panigrahi GB ，Edwards M ，Yu L ，Campbell BB ，Mandel A ，Zhang C ，Zhukova N ，Alharbi M ，Bernstein M ，Bowers DC ，Carroll S ，Cole KA ，Constantini S ，Crooks B ，Dvir R ，Farah R ，Hijiya N ，George B ，Laetsch TW ，Larouche V ，Lindhorst S ，Luiten RC ，Magimairajan V ，Mason G ，Mason W ，Mordechai O ，Mushtaq N ，Nicholas G ，Oren M ，Palma L ，Pedroza LA ，Ramdas J ，Samuel D ，Wolfe Schneider K ，Seeley A ，Semotiuk K ，Shamvil A ，Sumerauer D ，Toledano H ，Tomboc P ，Wierman M ，Van Damme A ，Lee YY ，Zapotocky M ，Bouffet E ，Durno C ，Aronson M ，Gallinger S ，Foulkes WD ，Malkin D ，Tabori U ，Pearson CE ... -  《-》

[Correlation between mismatch-repair protein expression and clinicopathologic features in 658 colorectal cancers].

Hu XR ，Xu C ，Kang Y ，Wang T ，Zhang Y ，Yang XH ... -  《-》

Muir-Torre Syndrome and founder mismatch repair gene mutations: A long gone historical genetic challenge.

A "cancer predisposing syndrome" later labeled as Hereditary Non-Polyposis Colorectal Cancer (HNPCC) or Lynch Syndrome, was firstly described by Warthin, about one century ago. An increased predisposition to the development of multiple familial tumors is described as characteristic of this syndrome where visceral and cutaneous malignancies may appear at an early age namely endometrial, gastric, small bowel, ureteral and renal pelvis, ovarian, hepatobiliary tract, pancreatic, brain (Turcot Syndrome) and sebaceous glands (Muir-Torre Syndrome). The latter, a variant of Lynch Syndrome, is characterized by the presence of sebaceous skin adenomas, carcinomas and/or keratoacanthomas associated with visceral malignancies. Both Lynch Syndrome and Muir-Torre Syndrome have been recognized due to germline mutations in mismatch repair genes MLH1, MSH2 and MSH6. To date, 56 Lynch Syndrome founder mutations dependent on MLH1, MSH2 and, although less frequently found, MSH6 and PMS2 are described. Some of these founder mutations, principally of MSH2 gene, have been described to cause Muir-Torre phenotype and have been traced in large and outbreed Muir-Torre Syndrome families living in different US and European territories. Due to the evidences of highly specific Muir-Torre phenotypes related to the presence of widespread MSH2 founder mutations, preliminary search for these MSH2 common mutations in individuals carrying sebaceous tumors and/or keratoacanthomas, at early age or in association to visceral and familial tumors, permits cost-effective and time-saving diagnostic strategies for Lynch/Muir-Torre Syndromes.

Ponti G ，Manfredini M ，Tomasi A ，Pellacani G ... -  《-》