Expression of neutral amino acid transporter ASCT2 in human prostate.
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+ semi-quantitation 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 nonmalignant 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.
Li
Rile
R
Department of Pathology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA.
Younes
Mamoun
M
Frolov
Anna
A
Wheeler
Thomas M
TM
Scardino
Peter
P
Ohori
Makoto
M
Ayala
Gustavo
G
D026962:Amino Acid Transport System ASC / Q000096:biosynthesis*; D015331:Cohort Studies; D018572:Disease-Free Survival; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D015778:Minor Histocompatibility Antigens; D011467:Prostate / Q000378:metabolism*; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy; D011470:Prostatic Hyperplasia / Q000097:blood / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D011471:Prostatic Neoplasms / Q000097:blood / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D012189:Retrospective Studies
D026962:Amino Acid Transport System ASC; D015778:Minor Histocompatibility Antigens; C420506:SLC1A5 protein, human; D017430:Prostate-Specific Antigen