Cytoplasmic MSH2 immunoreactivity in a patient with Lynch syndrome with an EPCAM-MSH2 fusion.

Shigeki Sekine, Reiko Ogawa, Shinya Saito, Mineko Ushiama, Dai Shida, Takeshi Nakajima, Hirokazu Taniguchi, Nobuyoshi Hiraoka, Teruhiko Yoshida, Kokichi Sugano

Histopathology 2017 Mar

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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. 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. 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. © 2016 John Wiley & Sons Ltd.

Citation

Shigeki Sekine, Reiko Ogawa, Shinya Saito, Mineko Ushiama, Dai Shida, Takeshi Nakajima, Hirokazu Taniguchi, Nobuyoshi Hiraoka, Teruhiko Yoshida, Kokichi Sugano. Cytoplasmic MSH2 immunoreactivity in a patient with Lynch syndrome with an EPCAM-MSH2 fusion. Histopathology. 2017 Mar;70(4):664-669