Protein Expression of ARID2, PIK3CA, p53 and β-Catenin in Hepatocellular Carcinoma (HCC) and Background Cirrhotic Liver
Jason C You, Hushan Yang, Lindsay Simon, Jen Au, Ashlie L Burkart. Thomas Jefferson University, Philadelphia, PA
Background: Available evidence suggests that HCCs are genetically heterogeneous tumors, yet the genetic events are not clearly understood. Recent molecular studies have detected ARID2 mutations in HCC and others have shown a possible association with viral etiology and cancer mutations in PIK3CA, p53 and β-catenin. However, studies evaluating these genetic events through protein expression are lacking.
Design: Immunohistochemistry was performed using ARID2, PIK3CA, p53, and β-catenin antibodies on HCC and background cirrhotic liver from 58 explanted livers.
Results: Diffuse loss of nuclear expression of ARID2 was observed in 4 of 58 (6.9%) HCCs and 13 of 57 (22.4%) HCCs showed nuclear expression of p53. β-catenin nuclear expression was observed in 5 of 57 (8.6%) HCCs. While PIK3CA expression was seen in all non-neoplastic cirrhotic livers at dilution of 1:200, 10 of 57 (17.2%) HCCs had complete loss of PIK3CA expression; the remaining 47 cases showed PIK3CA expression in both neoplastic and non-neoplastic tissue. Statistical analysis showed no association between the expression of the four proteins in HCC and the etiology of cirrhosis (all p>0.05). Protein expression was independent of each other (r2≤0.72). ARID2 inactivation had a significant association with cancer recurrence (p=0.042 multivariate adjusted) [figure 1] and occurred more frequently in non-Caucasians (P=0.049). p53 nuclear expression had a strong association with poor differentiation (P<0.0001) and tumor number (p=0.031). PIK3CA loss of expression in tumor was more common in patients with tumors that did not meet the Milan criteria at time of liver transplantation (P=0.049) and more common in non-Caucasians (P=0.033).
Conclusions: An association with viral etiology and protein expression was not observed. Protein expression was found to be independent of each other. This is the first study to show that loss of ARID2 expression in HCC is associated with cancer recurrence. In support of previous studies, p53 nuclear expression had a high association with poor differentiation and tumor number. Diffuse loss of expression of the oncoprotein PIK3CA in HCC is a novel finding and further investigations may determine if this represents feedback inactivation of the mTOR pathway.
Wednesday, March 6, 2013 1:00 PM
Poster Session VI # 122, Wednesday Afternoon