Expression of neutral amino acid transporter ASCT2 in human prostate

Document Type

Journal Article

Publication Date

7-1-2003

Journal

Anticancer Research

Volume

23

Issue

4

Keywords

ASCT2; Glutamine; Prognosis; Prostate cancer

Abstract

The neutral amino acid transporter ASCT2 has been associated with increased metabolism in malignant tumors. Its biological significance in tumor proliferation, progression, and its impact on cancer patients' survival remains largely unknown. Tissue microarray (TMA) technology was used to build arrays from 640 cases of radical prostatectomies (triplicate normal prostate, benign prostatic hyperplasia (BPH), and prostate adenocarcinoma (PCa)). Slides were immunostained with an antibody to ASCT2 and scored using a 0-3+ semiquantitation scoring system for both intensity and percentage. Correlation of ASCT2 expression with patients' clinical and pathological variables was analyzed by the Spearman correlation test. Kaplan-Meier analysis and log rank test were used to determine the probability of disease recurrence. Cox regression model was also used for multivariate analysis. 497 PCa had accessible data. ASCT2 was localized in the cytoplasm of epithelial cells of normal prostate, BPH and PCa. High-level expression of ASCT2 was significantly higher in normal tissues (49%) as compared to BPH (25.8%) or cancer (25.3%) (p<0.001). ASCT2 expression was weakly but significantly correlated with preoperative PSA (Pre-PSA), Gleason score (GS), lymph node status (LN) (p=0.019). ASCT2 expression was significantly associated with shorter time to biochemical recurrence only on univariate analysis (p=0.046). ASCT2 appears to be required for the glutamine metabolism in both non-malignant and malignant prostate. ASCT2-positive PCa seems to be related to a more aggressive biological behavior. ASCT 2 seems to be involved in tumor progression.

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