Ann Surg Treat Res.  2015 Feb;88(2):77-85. 10.4174/astr.2015.88.2.77.

Astrocyte elevated gene-1 overexpression in hepatocellular carcinoma: an independent prognostic factor

• Jung HI
• Ahn T
• Bae SH
• Chung JC
• Kim H
• Chin S
• Jeong D
• Cho HD
• Lee MS
• Kim HC
• Kim CH
• Baek MJ

• KMID: 1804124
• DOI: http://doi.org/10.4174/astr.2015.88.2.77

Abstract

PURPOSE
Astrocyte elevated gene-1 (AEG-1) plays important roles in tumorigenesis such as proliferation, invasion, metastasis, angiogenesis, and chemoresistance. We examined the expression of AEG-1 in patients with hepatocellular carcinoma (HCC).
METHODS
Eighty-five samples were collected from patients with HCC who underwent surgery and were histopathologically confirmed to have HCC. Two independent pathologists, experienced in evaluating immunohistochemistry and blinded to the clinical outcomes of the patients, reviewed all samples. They determined AEG-1 expression semiquantitatively by assessing the percentage of positively stained immunoreactive cells and staining intensity. Clinicopathological data were analyzed in association with prognosis.
RESULTS
The association was estimated by univariate and multivariate analyses with Cox regression. Tumor size (hazard ratio [HR], 2.285; 95% confidence interval [CI], 1.175-4.447; P = 0.015), microvascular invasion (HR, 6.754; 95% CI, 1.631-27.965; P = 0.008), and AEG-1 expression (HR, 4.756; 95% CI, 1.697-13.329; P = 0.003) were independent prognostic factors for overall survival. Those for disease-free survival rate were tumor size (HR, 2.245; 95% CI, 1.282-3.933; P = 0.005) and AEG-1 expression (HR, 1.916; 95% CI, 1.035-3.545; P = 0.038). The cumulative 5-year survival and recurrence rates were 89.2% and 50.0% in the low-expressing group and 24.5% and 82.4% in the high-expressing group, respectively.
CONCLUSION
The results suggest that AEG-1 overexpression could serve as a valuable prognostic marker in patients with HCC.

Keyword

Human MTDH protein; Hepatocellular carcinoma; Neoplasm metastasis

MeSH Terms

Astrocytes*
Carcinogenesis
Carcinoma, Hepatocellular*
Disease-Free Survival
Humans
Immunohistochemistry
Multivariate Analysis
Neoplasm Metastasis
Prognosis
Recurrence

Figure

• 

  Fig. 1 (A) Astrocyte elevated gene-1 (AEG-1) was not expressed in the cytoplasm of normal hepatocytes. (B) AEG-1 was mildly expressed in tumor cells of Edmondson and Steiner (ES) grade I hepatocellular carcinoma (HCC) (score, 1). (C) AEG-1 was moderately expressed in the cytoplasm of ES grade II HCC (score, 2). (D) AEG-1 was strongly expressed in the cytoplasm of ES grade III HCC (score, 3). (E) AEG-1 was strongly expressed in the cytoplasm of ES grade IV HCC (score, 3). (F) AEG-1 was strongly expressed in the cytoplasm of highly infiltrative HCC (score, 3). Scale: A-D, 50 µm; E-F, 100 µm.

• 

  Fig. 2 Overall (A) and disease-free survival (B) of all the patients with hepatocellular carcinoma (HCC) in the two astrocyte elevated gene-1 (AEG-1) expression groups. The 5-year overall (A) and disease-free survival (B) were 24.5% and 17.6% in the AEG-1 high expressing group (thick line) and 89.2% and 50% in the low AEG-1 expressing group (dotted line).

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