Alterations in the p16/pRb cell cycle checkpoint occur commonly in primary and metastatic human prostate cancer.
We examined the status of a cell cycle checkpoint by immunohistochemically staining for p16 and pRb using multiple tissue arrays generated from 49 primary and 23 hormone-sensitive metastatic human prostate cancers. We find that p16, a cell cycle inhibitor, is paradoxically overexpressed in 83% of proliferating primary prostate cancers and increased expression correlates with a more rapid treatment failure (P=0.01) and a higher histologic grade (P=0.001). pRb staining is heterogeneous, loses expression infrequently (19%), and does not correlate with p16 expression. Loss of either p16 or pRb expression is found significantly (P=0.01) more commonly (55%) in metastatic specimens. The remarkable frequency of p16/pRb alterations and strong clinical associations implicates inactivation of this pathway as a critical determinant in prostate cancer progression.
Jarrard
David F
DF
Department of Surgery, Section of Urology, K6/527 Clinical Science Center, 600 Highland Avenue, Madison, WI 53792, USA.
Modder
Joshua
J
Fadden
Paul
P
Fu
Vivian
V
Sebree
Linda
L
Heisey
Dennis
D
Schwarze
Steven R
SR
Friedl
Andreas
A
D000230:Adenocarcinoma / Q000737:chemistry / Q000235:genetics / Q000473:pathology*; D000368:Aged; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis*; D018450:Disease Progression; D018572:Disease-Free Survival; D016193:G1 Phase; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D016161:Genes, Retinoblastoma; D019942:Genes, p16; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000032:analysis*; D011471:Prostatic Neoplasms / Q000737:chemistry / Q000235:genetics / Q000473:pathology*; D016160:Retinoblastoma Protein / Q000032:analysis*
D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins; D016160:Retinoblastoma Protein