Korean J Pathol.
2014 Aug;48(4):276-282. 10.4132/KoreanJPathol.2014.48.4.276.
Differential Features of Microsatellite-Unstable Colorectal Carcinomas Depending on EPCAM Expression Status
- Affiliations
-
- 1Department of Pathology, SMG-SNU Boramae Medical Center, Seoul, Korea.
- 2Department of Pathology, Seoul National University College of Medicine, Seoul, Korea. ghkang@snu.ac.kr
- 3Laboratory of Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
- 4Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Korea.
- KMID: 1719561
- DOI: http://doi.org/10.4132/KoreanJPathol.2014.48.4.276
Abstract
- BACKGROUND
Recent studies have revealed that a small subset of Lynch syndrome-associated colorectal carcinomas (CRCs) is caused by a germline EPCAM deletion-induced MSH2 epimutation. Based on the finding of this genetic alteration, we investigated the implications of EPCAM expression changes in microsatellite instability-high (MSI-H) CRCs.
METHODS
Expression of EPCAM and DNA mismatch repair proteins was assessed by immunohistochemistry in 168 MSI-H CRCs. Using DNA samples of these tumors, MLH1 promoter methylation status was also determined by methylation-specific real-time polymerase chain reaction method (MethyLight).
RESULTS
Among 168 MSI-H CRCs, complete loss (CL) and focal loss (FL) of EPCAM expression was observed in two (1.2%) and 22 (13.1%) cases, respectively. Both of the EPCAM-CL cases were found in MSH2-negative tumors without MLH1 promoter methylation. However, only nine of the 22 EPCAM-FL tumors had MSH2 deficiency. Of the 22 EPCAM-FL tumors, 13 showed MLH1 loss, and among them, nine cases were determined to have MLH1 methylation. EPCAM-FL was significantly associated with advanced stage (p=.043), distant metastasis (p=.003), poor differentiation (p=.001), and signet ring cell component (p=.004).
CONCLUSIONS
Loss of EPCAM expression is differentially associated with clinicopathological and molecular features, depending on the completeness of the loss, in MSI-H CRCs.
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