Mismatch Repair Status in Seventy Biliary Tract Carcinomas
WL Frankel, JJ Liu, H Hampel, AM Bellizzi. The Ohio State University Medical Center, Columbus, OH; Brigham and Women's Hospital, Boston, MA
Background: Lynch Syndrome (LS) is a cancer predisposition syndrome due to germline mutations in DNA mismatch repair (MMR) genes. Deficient MMR function results in microsatellite unstable tumors. In addition to colon cancer, there is increased risk of cancer at a defined subset of extracolonic sites, including the biliary tract. Population-based LS screening by MMR immunohistochemistry (IHC) is effective in colon cancer, and LS-colon cancers are associated with certain histologic features. We studied the MMR status of a group of biliary tract carcinomas unselected for age or personal cancer history.
Design: Tissue microarrays were constructed from 47 cholangiocarcinomas (CC) and 23 gallbladder adenocarcinomas (GB). MMR IHC for MLH1, PMS2, MSH2, and MSH6 was performed. The proteins were scored as present or absent (no definite nuclear staining in the setting of intact staining in internal control). Clinical data (age, sex, personal history of cancer) was collected and histologic features (grade, presence of tumor infiltrating lymphocytes or mucinous features) assessed in patients with abnormal MMR IHC.
Results: Two of 47 (4.3%) cholangiocarcinomas (2 women, ages 70, 75) and 1 of 23 (4.3%) gallbladder adenocarcinomas (woman, 62) demonstrated absent MLH1/PMS2 expression. All were moderately differentiated adenocarcinomas without tumor infiltrating lymphocytes (TIL) or mucinous features. The patient with the GB had concurrent clear cell renal cell carcinoma; the 2 patients with CC had no known history of malignancy.
Conclusions: Biliary tumors demonstrate a low rate of deficient MMR function (4.3%). Patterns of abnormal IHC especially suggestive of LS (i.e., absent MSH2/MSH6 expression, isolated loss of PMS2 or MSH6) were not observed. The 3 abnormal cases lacked features of microsatellite unstable tumors as seen in the colon (i.e., poor differentiation, TIL, mucinous features). Absent MLH1/PMS2 expression in rare tumors may reflect MLH1 promoter hypermethylation. Population-based screening of CC and GB does not appear warranted. Instead, testing of select cases (e.g. those with compelling histologic features; instances in which one represents the only tumor tissue available in a family with suggestive family history) is recommended.
Category: Liver & Pancreas
Tuesday, March 23, 2010 1:00 PM
Poster Session IV # 189, Tuesday Afternoon