Germline deletions affecting the
epithelial cell adhesion molecule (
EPCAM) gene lead to silencing of MSH2 and cause
Lynch syndrome. We have recently reported that lack of
EPCAM expression occurs in many, but not all
tumors from
Lynch syndrome patients with
EPCAM germline deletions. The differences in
EPCAM expression were not related to the localization of
EPCAM germline deletions. We therefore hypothesized that the type of the second somatic hit, which leads to MSH2 inactivation during
tumor development, determines
EPCAM expression in the
tumor cells. To test this hypothesis and to evaluate whether lack of
EPCAM expression can already be detected in
Lynch syndrome-associated
adenomas, we analyzed four
carcinomas and two
adenomas from
EPCAM germline deletion carriers for
EPCAM protein expression and allelic deletion status of the
EPCAM gene region by multiplex
ligation-dependent probe amplification. In four out of six
tumors we observed lack of
EPCAM expression accompanied by biallelic deletions affecting the
EPCAM gene. In contrast, monoallelic retention of the
EPCAM gene was observed in the remaining two
tumors with retained
EPCAM protein expression. These results demonstrate that
EPCAM expression in
tumors from
EPCAM deletion carriers depends on the localization of the second somatic hit that inactivates MSH2. Moreover, we report lack of
EPCAM protein expression in a colorectal
adenoma, suggesting that
EPCAM immunohistochemistry may detect
EPCAM germline deletions already at a precancerous stage.