Dysregulation of annexin I protein expression in high-grade prostatic intraepithelial neoplasia and prostate cancer.
OBJECTIVE
To determine expression levels of annexin I (lipocortin I) in patient-matched benign prostatic epithelium (BPE), high-grade prostatic intraepithelial neoplasia (HGPIN), and prostate cancer (CaP). EXPERIMETNAL DESIGN: Annexin I protein expression was examined with a standard immunohistochemical protocol in 69 radical prostatectomy specimens, 45 of which also contained HGPIN. Immunostained sections were scored visually by a genitourinary pathologist and mean optical density was measured with digital image analysis. Real-time fluorescence quantitative PCR was used to measure expression levels of annexin I mRNA in patient-matched CaP and BPE from 14 snap-frozen, radical prostatectomy specimens.


RESULTS
Annexin I protein expression was reduced in 91% (41/45) of HGPIN lesions and 94% (65/69) of invasive CaP compared with BPE in the same histological section when assessed visually. Mean absorbance was reduced significantly (P < 0.05) in 97.7% (44/45) of HGPIN lesions and 98.5% (68/69) of CaP glands compared with BPE. In 79% of cases (11/14; P < 0.05), mRNA expression was reduced in CaP as compared with patient-matched BPE. Annexin I mRNA and protein expression levels did not correlate with Gleason grade, pathological stage, or race.


CONCLUSIONS
Down-regulation of annexin I protein expression is a common finding in HGPIN and CaP, suggesting that annexin I dysregulation may be an important early event in CaP initiation. Because mRNA levels are reduced in a high proportion of cases, one likely mechanism for annexin I dysregulation occurs at the level of gene transcription. Results of these studies support a valuable role for a molecular profiling approach to CaP research.
Kang
John S
JS
Department of Surgery, Divisions of Urology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Calvo
Benjamin F
BF
Maygarden
Susan J
SJ
Caskey
Laura S
LS
Mohler
James L
JL
Ornstein
David K
DK
D017305:Annexin A1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011468:Prostatectomy; D019048:Prostatic Intraepithelial Neoplasia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism
D017305:Annexin A1; D012333:RNA, Messenger