title: Cytoplasmic MSH2 immunoreactivity in a patient with Lynch syndrome with an EPCAM-MSH2 fusion.
abstract: OBJECTIVE
  Immunohistochemistry for mismatch repair (MMR) proteins is being increasingly used to examine MMR status in tumours. The aim of the present article was to report the case of a colon cancer patient with Lynch syndrome who showed unusual cytoplasmic MMR protein localization.
  
  
  RESULTS
  Histologically, the colon cancer was diagnosed as medullary carcinoma associated with prominent tumour-infiltrating lymphocytes and a Crohn's-like reaction. Immunohistochemistry revealed cytoplasmic and nuclear expression of MSH2 in non-neoplastic cells, and exclusively cytoplasmic expression in tumour cells. MSH6 expression was nuclear in non-neoplastic cells, but was lost in tumour cells. Nuclear expression of MLH1 and PMS2 was retained in both non-neoplastic and tumour cells. The tumour was microsatellite instability-high, which is indicative of defective MMR function. A subsequent germline mutation analysis identified a genomic deletion spanning the 3' region of EPCAM and the 5' region of MSH2, resulting in an in-frame fusion of EPCAM and MSH2.
  
  
  CONCLUSIONS
  The unusual cytoplasmic immunoreactivity of MSH2 was considered to be attributable to the non-functional EPCAM-MSH2 fusion product. The present case illustrates that not only loss of expression, but also abnormal localization, of MMR proteins is indicative of a defective MMR system.
authors.affiliation: Division of Pathology and Clinical Laboratories, National Cancer Centre Hospital, Tokyo, Japan.|Molecular Pathology Division, National Cancer Centre Research Institute, Tokyo, Japan.|Department of Genetic Medicine and Services, National Cancer Centre Hospital, Tokyo, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Sekine
authors.affiliation: Molecular Pathology Division, National Cancer Centre Research Institute, Tokyo, Japan.
authors.forename: Reiko
authors.initials: R
authors.lastname: Ogawa
authors.affiliation: Oncogene Research Unit/Cancer Prevention Unit, Tochigi Cancer Centre Research Institute, Tochigi, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Saito
authors.affiliation: Department of Genetic Medicine and Services, National Cancer Centre Hospital, Tokyo, Japan.|Division of Genetics, National Cancer Centre Research Institute, Tokyo, Japan.
authors.forename: Mineko
authors.initials: M
authors.lastname: Ushiama
authors.affiliation: Division of Colorectal Surgery, National Cancer Centre Hospital, Tokyo, Japan.
authors.forename: Dai
authors.initials: D
authors.lastname: Shida
authors.affiliation: Department of Genetic Medicine and Services, National Cancer Centre Hospital, Tokyo, Japan.|Division of Endoscopy, National Cancer Centre Hospital, Tokyo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nakajima
authors.affiliation: Division of Pathology and Clinical Laboratories, National Cancer Centre Hospital, Tokyo, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Taniguchi
authors.affiliation: Division of Pathology and Clinical Laboratories, National Cancer Centre Hospital, Tokyo, Japan.|Molecular Pathology Division, National Cancer Centre Research Institute, Tokyo, Japan.|Department of Genetic Medicine and Services, National Cancer Centre Hospital, Tokyo, Japan.
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Hiraoka
authors.affiliation: Department of Genetic Medicine and Services, National Cancer Centre Hospital, Tokyo, Japan.|Division of Genetics, National Cancer Centre Research Institute, Tokyo, Japan.
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Yoshida
authors.affiliation: Department of Genetic Medicine and Services, National Cancer Centre Hospital, Tokyo, Japan.|Oncogene Research Unit/Cancer Prevention Unit, Tochigi Cancer Centre Research Institute, Tochigi, Japan.
authors.forename: Kokichi
authors.initials: K
authors.lastname: Sugano
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics* / Q000473:pathology; D003593:Cytoplasm / Q000378:metabolism; D000071858:Epithelial Cell Adhesion Molecule / Q000235:genetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D051718:MutS Homolog 2 Protein / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D050596:Oncogene Fusion / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; C497172:MSH2 protein, human; D051718:MutS Homolog 2 Protein
keywords: EPCAM; Lynch syndrome; MSH2; fusion; immunohistochemistry