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 p 16 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. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.