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Subcellular localization of APE1/Ref-1 in human hepatocellular carcinoma: possible prognostic significance.


ABSTRACT: APE1/Ref-1, normally localized in the nucleus, is a regulator of the cellular response to oxidative stress. Cytoplasmic localization has been observed in several tumors and correlates with a poor prognosis. Because no data are available on liver tumors, we investigated APE1/Ref-1 subcellular localization and its correlation with survival in 47 consecutive patients undergoing hepatocellular carcinoma (HCC) resection. APE1/Ref-1 expression was determined by immunohistochemistry in HCC and surrounding liver cirrhosis (SLC) and compared with normal liver tissue. Survival probability was evaluated using Kaplan-Meier curves (log-rank test) and Cox regression. Cytoplasmic expression of APE1/Ref-1 was significantly higher in HCC than in SLC (P = 0.00001); normal liver showed only nuclear reactivity. Patients with poorly differentiated HCC showed a cytoplasmic expression three times higher than those with well-differentiated HCC (P = 0.03). Cytoplasmic localization was associated with a median survival time shorter than those with negative cytoplasmic reactivity (0.44 compared with 1.64 years, P = 0.003), and multivariable analysis confirmed that cytoplasmic APE1/Ref-1 localization is a predictor of survival. Cytoplasmic expression of APE1/Ref-1 is increased in HCC and is associated with a lower degree of differentiation and a shorter survival time, pointing to the use of the cytoplasmic localization of APE1/Ref-1 as a prognostic marker for HCC.

SUBMITTER: Di Maso V 

PROVIDER: S-EPMC1869623 | biostudies-literature | 2007 Jan-Feb

REPOSITORIES: biostudies-literature

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Subcellular localization of APE1/Ref-1 in human hepatocellular carcinoma: possible prognostic significance.

Di Maso Vittorio V   Avellini Claudio C   Crocè Lory Saveria LS   Rosso Natalia N   Quadrifoglio Franco F   Cesaratto Laura L   Codarin Erika E   Bedogni Giorgio G   Beltrami Carlo Alberto CA   Tell Gianluca G   Tiribelli Claudio C  

Molecular medicine (Cambridge, Mass.) 20070101 1-2


APE1/Ref-1, normally localized in the nucleus, is a regulator of the cellular response to oxidative stress. Cytoplasmic localization has been observed in several tumors and correlates with a poor prognosis. Because no data are available on liver tumors, we investigated APE1/Ref-1 subcellular localization and its correlation with survival in 47 consecutive patients undergoing hepatocellular carcinoma (HCC) resection. APE1/Ref-1 expression was determined by immunohistochemistry in HCC and surround  ...[more]

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