ARID2, p110 alpha, p53, and beta-catenin protein expression in hepatocellular carcinoma and dinicopathologic implications

作者：You Jason; Yang Hushan; Lai Yinzhi; Simon Lindsay; Au Jen; Burkart Ashlie L^*

来源：Human Pathology, 2015, 46(4): 583-592.

DOI：10.1016/j.humpath.2015.01.001

• Immunohistochemistry
• Hepatocatcinogenesis
• mTOR
• Oncoprotein
• Recurrence

AT-rich interactive domain 2 (ARLD2), catenin (cadherin-associated protein), beta 1, 881cDa (beta-catenin), tumor protein 53 (p53), and phosphatidylinositol-4,5-bisphosphate 3-lcinase, catalytic subunit alpha (p110 alpha) mutations are implicated in hepatocellular carcinoma (HCC); and previous work has contributed to thorough molecular characterization of these events. However, studies that assess the impact of these mutations on downstream protein expression, especially those that evaluate all 4 cancer markers simultaneously, are relatively lacking. Hence, the present study uses immuriohistochemistry to assess protein expression patterns of ARID2, beta-catenin, p53, and p110 alpha in HCCs and adjacent nonneoplastic cirrhotic tissues from 58 explanted livers. Notably, this study is the first to our knowledge to investigate ARID2 protein expression in the liver. The frequency of ARDD2 mutations detected using our immunohistochemistry method was similar to that reported in previous molecular studies. Furthermore, we found that loss of ARED2 protein expression may be associated with recurrence, although further studies must be done to validate these findings in a larger population. We found that expression patterns of the 4 cancer markers were independent of each other, suggesting separate pathways of hepatocarcinogenesis. We also did not observe an association between viral etiology and protein expression. Consistent with previous studies, overexpression of p53 correlated with poor differentiation. Lastly, 17.5% of HCCs paradoxically had diffuse loss of the oncoprotein p110 alpha compared with strong expression in background cirrhotic liver. The exact mechanism is unclear, but enigmatic loss of oncoprotein function has been described in other carcinomas and could potentially have significant implications for the use of targeted mechanistic target of rapamycin (serine/threonine kinase) drug therapies.

• 出版日期2015-4