BRUCE: A Novel Protein Associated with Carcinogenesis of Liver and Potential Marker for Differential Diagnosis
Ravi Patel, Jing Lu, Chunying Du, Jiang Wang. University of Cincinnati College of Medicine, Cincinnati, OH
Background: BRUCE is a recently found protein with multifunction. One of its functions is to regulate cell division, and reduction in the levels of BRUCE protein by gene silencing results in aneuploid cells. However, it is unknown whether such reduction associates with human liver tumors and if so, whether it can be used as a differential diagnostic and prognostic marker for patients with liver lesions.
Design: Thirty two resections or biopsy cases of human liver mass lesions were studied. The specimens include 18 HCC, 9 adenomas and 5 focal nodular hyperplasia (FNH). Ten HCC cases have cirrhotic background and the remaining 8 do not. Immunohistochemistry was performed using an anti-BRUCE monoclonal antibody. The percentage and intensity (0-3) of the positivity in both lesional and non-lesional hepatocytes were evaluated and scored.
Results: BRUCE protein is detected in the cytoplasm of hepatocytes. All HCCs (100%) show decreased expression of BRUCE at various levels, of which 13/18 (72%) cases have negative stain in more than 50% of tumor cells and the remaining 5 tumors totally lost BRUCE expression. All adenomas and FNHs express BRUCE with 100% of cell positivity for all cases. All cases of hepatocytes adjacent to HCC in either cirrhotic or non-cirrhotic livers show 100% of positivity except 1 cirrhotic liver has 90% of cell stain. The intensity of positive stain varies in non-lesional hepatocyte, FNH, adenoma and HCC; however, the majority (17/23, 74%) of hepatocytes in non-lesional areas have strong (3+) positivity while most (9/13, 69%) of positive HCC show weak (1+) expression and remaining 4 cases are intermediately (2+) positive. 11/14 (79%) of adenoma and FNH have intermediate (2+) or strong (3+) positivity. Loss of BRUCE expression is not associated with the grade and stage of HCC.
Conclusions: The present study, for the first time, demonstrates that loss of BRUCE expression is associated with the development of human HCC. The finding also strongly suggests that BRUCE negative stain may be used as a specific marker to distinguish well-differentiated HCC from benign liver mass lesions, especially for difficult needle biopsy specimens. Further study with a larger number of specimens is needed to confirm our finding, investigate correlation of BRUCE with different etiology, therapeutic response, and survival.
Tuesday, March 20, 2012 9:30 AM
Poster Session III # 242, Tuesday Morning