Analysis of EPCAM Expression in Lynch Syndrome Associated Neoplasia
Michael A DiMaio, Shirley Kwok, Teri A Longacre. Stanford University Medical Center, Stanford, CA
Background: Lynch syndrome is an inherited tumor predisposition syndrome due to defective expression of DNA mismatch repair enzymes, leading to microsatellite instability. Affected individuals have increased risk of developing colorectal, uterine, and sebaceous neoplasms. Mutations in MLH1 and MSH2 account for most cases, but deletions of the 3' end of EPCAM, located upstream of MSH2, have been implicated in approximately 20% of cases with MSH2 loss. Some studies have suggested significantly lower incidence of uterine neoplasia in this variant of Lynch syndrome. Loss of EPCAM protein expression has been observed in colorectal tumors associated with EPCAM deletion; however, no studies have characterized the expression of EPCAM protein in MSH2 deficient Lynch syndrome neoplasia other than colorectal tumors.
Design: A total of 288 colorectal, 481 uterine, and 56 sebaceous tumors were analyzed for MSH2, MSH6, MLH1, and PMS2 expression by immunohistochemistry. EPCAM immunohistochemistry was performed on tumors with loss of MSH2 as well tissue microarrays containing 251 colorectal and 62 uterine adenocarcinomas not associated with Lynch syndrome.
Results: 33 tumors from unique patients showed loss of MSH2 (7 sebaceous neoplasms, 17 uterine carcinomas, and 9 colorectal carinomas). EPCAM expression results for these tumors and Non-Lynch syndrome tumors are shown in Table 1. Tumors with membranous expression of EPCAM were scored as positive.
|Tumors||EPCAM expression by IHC (%)|
|Non Lynch syndrome colorectal carcinoma||251/251 (100)|
|Non Lynch syndrome uterine carcinoma||62/62 (100)|
|MSH2 negative sebaceous neoplasms||0/7 (0)|
|MSH2 negative colorectal carcinoma||8/9 (89)|
|MSH2 negative uterine carcinoma||16/17 (94)|