Altered N-myc downstream-regulated gene 1 protein expression in African-American compared with caucasian prostate cancer patients.
OBJECTIVE
The protein encoded by N-myc downstream-regulated gene 1 (NDRG1) is a recently discovered protein whose transcription is induced by androgens and hypoxia. We hypothesized that NDRG1 expression patterns might reveal a biological basis for the disparity of clinical outcome of prostate cancer patients with different ethnic backgrounds.


METHODS
Patients who underwent radical prostatectomy between 1990 and 2000 at Veterans Administration Medical Center of New York were examined. We studied 223 cases, including 157 African Americans and 66 Caucasians (T2, n = 144; >/=T3, n = 79; Gleason <7, n = 122; >/=7, n = 101). Three patterns of NDRG1 expression were identified in prostate cancer: (a) intense, predominately membranous staining similar to benign prostatic epithelium; (b) intense, nucleocytoplasmic localization; and (c) low or undetectable expression. We then examined the correlations between patients' clinicopathological parameters and different NDRG1 expression patterns.


RESULTS
In this study of patients with equal access to care, African-American ethnic origin was an independent predictor of prostate-specific antigen recurrence (P < 0.05). We also observed a significant correlation between different patterns of NDRG1 expression and ethnic origin. Pattern 2 was less frequent in African Americans (21% versus 38%), whereas the reverse was observed for pattern 3 (60% in African Americans versus 44% in Caucasians; P = 0.03). This association remained significant after controlling for both grade and stage simultaneously (P = 0.02).


CONCLUSIONS
Our data suggest that different NDRG1 expression patterns reflect differences in the response of prostatic epithelium to hypoxia and androgens in African-American compared with Caucasian patients. Further studies are needed to determine the contribution of NDRG1 to the disparity in clinical outcome observed between the two groups.
Caruso
Robert P
RP
Department of Urology, New York University Cancer Institute, Kaplan Comprehensive Cancer Center, New York, USA.
Levinson
Benjamin
B
Melamed
Jonathan
J
Wieczorek
Rosemary
R
Taneja
Samir
S
Polsky
David
D
Chang
Caroline
C
Zeleniuch-Jacquotte
Anne
A
Salnikow
Konstantin
K
Yee
Herman
H
Costa
Max
M
Osman
Iman
I
D001741:Black or African American / Q000208:ethnology*; D000368:Aged; D000369:Aged, 80 and over; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011468:Prostatectomy; D011470:Prostatic Hyperplasia / Q000208:ethnology / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000208:ethnology / Q000378:metabolism*; D012189:Retrospective Studies; D044465:White People / Q000208:ethnology*; D000099259:N-myc Downstream-Regulated Gene 1 Protein
D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; D017430:Prostate-Specific Antigen; D000099259:N-myc Downstream-Regulated Gene 1 Protein