@article{oai:air.repo.nii.ac.jp:00003074,
 author = {Kato, Aya and Sato, Naoki and Sugawara, Tae and Takahashi, Kazue and Kito, Masahiko and Makino, Kenichi and Sato, Toshiharu and Shimizu, Dai and Shirasawa, Hiromitu and Miura, Hiroshi and Sato, Wataru and Kumazawa, Yukiyo and Sato, Akira and Kumagai, Jin and Terada, Yukihiro},
 issue = {6},
 journal = {American Journal of Surgical Pathology},
 month = {},
 note = {Lynch syndrome (LS) is an autosomal dominant inherited disorder mainly caused by a   germline  mutation in the DNA mismatch repair (MMR) genes (MLH1, MSH2, MSH6, PMS2) and is   associated with  increased risk of various cancers, particularly colorectal cancer and endometrial   cancer (EC).  Women with LS account for 2–6% of EC patients; it is clinically important to identify   LS in such  individuals for predicting and/or preventing additional LS-associated cancers. PMS2   germline  mutation (PMS2-LS) is the rarest contribution to LS etiology among the four LS-  associated MMR  germline mutations, and its detection is complicated. Therefore, prudent screening for   PMS2-LS is  important as it leads to an efficient LS-identification strategy. Immunohistochemistry   (IHC) is  recommended as a screening method for LS in EC. Isolated loss of PMS2 expression (IL-  PMS2) is  caused not only by PMS2-LS but also by MLH1 germline mutation or MLH1 promoter   hypermethylation  (MLH-PHM). This study aimed to determine the association between MLH1-PHM and IL-PMS2   to avoid  inappropriate genetic analysis. We performed MLH1 methylation analysis and MLH1/PMS2   germline  mutation testing for the IL-PMS2 cases. By performing MMR-IHC for 360 unselected ECs,   we selected  eight (2.2%) cases as IL-PMS2. Heterogeneous MLH1 staining and MLH1-PHM were detected   in 4/8 (50%)  IL-PMS2 tumors. Out of five IL-PMS2 patients who underwent genetic analysis, one had   PMS2 germline  mutation with normal MLH1 expression (without MLH1-PHM) and no MLH1 germline mutation   was detected.  We suggest that MLH1 promoter methylation analysis for IL-PMS2 EC should be performed   to exclude  sporadic cases prior to further PMS2 genetic testing.},
 pages = {770--776},
 title = {Isolated loss of PMS2 immunohistochemical expression is frequently caused by   heterogeneous MLH1  promoter hypermethylation in Lynch syndrome screening for endometrial cancer patients},
 volume = {40},
 year = {2016}
}