Cytoplasmic MSH2 immunoreactivity in a patient with Lynch syndrome with an EPCAM-MSH2 fusion.
Histopathology
; 70(4): 664-669, 2017 Mar.
Article
in En
| MEDLINE
| ID: mdl-27896849
ABSTRACT
AIMS:
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. METHODS ANDRESULTS:
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.Key words
Full text:
1
Database:
MEDLINE
Main subject:
Colorectal Neoplasms, Hereditary Nonpolyposis
/
Biomarkers, Tumor
/
MutS Homolog 2 Protein
Type of study:
Prognostic_studies
Limits:
Adult
/
Female
/
Humans
Language:
En
Journal:
Histopathology
Year:
2017
Type:
Article
Affiliation country:
Japan