p16 Is upregulated in proliferative inflammatory atrophy of the prostate.
BACKGROUND
Proliferative inflammatory atrophy (PIA) of the prostate is a common histological finding that has been postulated to be associated with prostate cancer. We examine PIA lesions for the expression of p16/CDKN2, a cyclin-dependent kinase inhibitor frequently altered in prostate cancer.


METHODS
Within tissues from two independent patient populations ("Test Set" and "Validation Set") undergoing radical prostatectomy, PIA lesions were identified and subjected to immunohistochemical staining for p16. Atrophic epithelial cells and regional normal epithelium were scored for the extent of p16 staining. In the Test Set, staining was also performed for the proliferation marker Ki-67. Double label immunofluorescence was employed to co-localize staining for p16 and Ki-67.


RESULTS
p16 expression was elevated in PIA in both data sets compared to normal epithelium (mean percent of cells staining positive in PIA = 11.1%-16.2%; mean percent of cells staining positive in normal = 0.6%-1.3%) (P = 0.0001). As expected from prior studies, the mean Ki-67 index was higher in PIA lesions (mean 8.2% staining positive) versus normal epithelium (mean 1.9% staining positive) (P = 0.0001), and the extent of staining for p16 correlated with Ki-67 (r = 0.7, P < 0.0001). However, co-localization immunofluorescent studies did not demonstrate staining for nuclear p16 and Ki-67 in the same cells.


CONCLUSIONS
Increased p16 expression accompanies increased cell proliferation in PIA lesions of the prostate. Yet, on the individual cell level, the upregulation of p16 in PIA lesions appears to represent a non-proliferative stress response, possibly to oxidative damage.
Faith
Dennis
D
Department of Pathology, The Sydney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA.
Han
Steven
S
Lee
Daniel K
DK
Friedl
Andreas
A
Hicks
Jessica L
JL
De Marzo
Angelo M
AM
Jarrard
David F
DF
D000368:Aged; D001284:Atrophy; D049109:Cell Proliferation; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis*; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000473:pathology; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D008875:Middle Aged; D011467:Prostate / Q000737:chemistry* / Q000473:pathology*; D015854:Up-Regulation
D019941:Cyclin-Dependent Kinase Inhibitor p16; D019394:Ki-67 Antigen