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. 2015 Feb 1;8(2):1878-88.
eCollection 2015.

Nuclear C-MYC expression level is associated with disease progression and potentially predictive of two year overall survival in prostate cancer

Affiliations

Nuclear C-MYC expression level is associated with disease progression and potentially predictive of two year overall survival in prostate cancer

Wen Zeng et al. Int J Clin Exp Pathol. .

Abstract

Purpose: Upregulation of nuclear C-MYC protein has been reported to be an early event in prostate cancer (PCa); however, its clinicopathological and prognostic significance remain controversial. We determined the association of nuclear C-MYC protein expression with clinicopathological parameters, prognosis, ETS-related gene (ERG) expression, and TMPRSS2-ERG status in PCa.

Methods: Nuclear C-MYC and ERG expression by immunohistochemistry and TMPRSS2-ERG status by triple-color probe fluorescence in situ hybridization assay were determined in 50 hormone-naïve PCa patients and 31 radical prostatectomy specimens.

Results: Nuclear C-MYC immunostaining was negative, positive, and strong positive in 27.5%, 32.5%, and 40.0% of cases, respectively. C-MYC immunostaining was significantly associated with clinical T stage (P < 0.001), distant metastasis at the time of diagnosis (P < 0.001) and TMPRSS2-ERG status (P = 0.001) but not with ERG immunostaining (P = 0.818). In the Kaplan-Meier analysis, C-MYC positive cases were found to have worse 2-year OS compared with C-MYC negative cases (P = 0.027). However, in the univariate Cox analysis, only TMPRSS2-ERG status (hazard ratio [HR] 0.189, 95% CI 0.057-0.629; P = 0.007) and distant metastasis (HR 3.545, 95% CI 1.056-11.894; P = 0.040) were significantly associated with 2-year OS. After adjusting for these two factors, TMPRSS2-ERG status still impacted 2-year OS (HR 0.196, 95% CI 0.049-0.778; P = 0.020).

Conclusions: Nuclear C-MYC overexpression may be associated with disease progression and potentially predictive of 2-year OS in PCa. This is the first study to demonstrate an association between nuclear C-MYC immunostaining and TMPRSS2-ERG status in PCa.

Keywords: C-MYC; ERG; TMPRSS2-ERG; immunohistochemistry; prostate cancer.

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Figures

Figure 1
Figure 1
Representative ERG negative (A), ERG heterogeneous (B), ERG positive (C), C-MYC negative (D; QS = 0), C-MYC positive (E; QS = 1~3), and C-MYC strong positive (F; QS = 4~6) immunostaining (400 ×). QS, quick score.
Figure 2
Figure 2
A. Schematic map of ‘TMPRSS2’ and ‘ERG’ gene region on 21q22. Red, blue and green signal represents the distal TMPRSS2, proximal TMPRSS2 and proximal ERG gene region, respectively. B-E. Represent four different TMPRSS2-ERG patterns identified in this study.

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