[1128] 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.

EPCAM Expression in MSH2 Negative Lynch Syndrome and Non-Lynch Syndrome Tumors
TumorsEPCAM expression by IHC (%)
Non Lynch syndrome colorectal carcinoma251/251 (100)
Non Lynch syndrome uterine carcinoma62/62 (100)
MSH2 negative sebaceous neoplasms0/7 (0)
MSH2 negative colorectal carcinoma8/9 (89)
MSH2 negative uterine carcinoma16/17 (94)

Conclusions: EPCAM is universally and strongly expressed in colorectal and uterine neoplasms not associated with Lynch syndrome. Loss of EPCAM expression is seen in 11% of MSH2 negative colorectal carcinoma and 6% of MSH2 negative uterine carcinoma. To our knowledge, this is the first demonstration of EPCAM loss in Lynch syndrome related uterine carcinoma. EPCAM immunohistochemistry may be useful in further classifying Lynch syndrome in patients with loss of MSH2 in colorectal and uterine neoplasms. EPCAM immunohistochemistry is not useful in workup of sebaceous neoplasms with MSH2 loss as these tumors are universally negative.
Category: Gynecologic & Obstetrics

Monday, March 4, 2013 9:30 AM

Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 174, Monday Morning


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