Aldo-Ketoreductase Family 1 B10 (AKR1B10) Protein as a Unique Malignant Biomarker To Distinguish Benign Liver Lesions from Hepatocellular Carcinoma
Kristina A Matkowskyj, Jie Liao, Haonan Li, Han Bai, M Sambasiva Rao, Reed A Omary, Guang-Yu Yang. Northwestern University, Chicago, IL
Background: AKR1B10 contributes to detoxification of xenobiotics by lipid peroxidation and metabolizes physiological substrates such as farnesal, retinal and carbonyls. Metabolizing these lipid substrates plays a crucial role in promoting carcinogenesis. AKR1B10 was first isolated from hepatocellular carcinoma (HCC) and further identified to be over-expressed in many cancers from various organs. In the present study, we performed an immunohistochemical (IHC) analysis to determine the prevalence/pattern of AKR1B10 expression in HCC, its usefulness to differentiate benign liver lesions from HCC, and to correlate with etiology and tumor response rates in order to identify a reliable biomarker to predict malignancy and chemosensitivity.
Design: Explanted livers with HCC with or without chemoembolization therapy (n=58) were retrieved from an achieved pathology database. Pathology reports and slides were reviewed to establish tumor response rate and correlated with AKR1B10 expression and therapy regimen. The etiologies of HCC included Hepatitis B and C, autoimmune hepatitis, steatohepatitis, alcohol, and cryptogenic cirrhosis. Benign hepatic lesions including focal nodular hyperplasia (FNH) (n=8) and hepatic adenoma (n=21), as well as HCC arising in an adenoma (n=3) were also included. IHC was performed using a monoclonal mouse AKR1B10 antibody and the avidin-biotin-peroxidase approach. Positive staining was defined as granular, cytoplasmic staining. The staining was further classified as no staining (0-10%), minimal (10-50%), moderate (50-75%) and high (>75%).
Results: Strong expression of AKR1B10 was observed in 87.9% (51/58) of HCC, but not adjacent normal/cirrhotic tissue (see Panel A). Greater than 75.8% of tumors (44/58) demonstrated high levels of expression (see Panel B). There was no correlation between the etiology of HCC or tumor response rates/therapeutic regimen with the extent of AKR1B10 expression. No expression of AKR1B10 was detected in cases of adenoma or FNH. In contrast, AKR1B10 was expressed in 66.7% (2/3) of HCC arising in the setting of adenoma, but only in the malignant component (see Panel C).
Conclusions: AKR1B10 expression levels in HCC are high irrespective of tumor etiology and tumor response rates. This finding likely explains why HCC is often unresponsive to chemotherapeutic/interventional approaches. Moreover, AKR1B10 expression can be used to reliably differentiate between benign and malignant primary lesions of the liver.
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 268, Monday Morning