Alterations in the p16/pRb cell cycle checkpoint occur commonly in primary and metastatic human prostate cancer

Cancer Lett. 2002 Nov 28;185(2):191-9. doi: 10.1016/s0304-3835(02)00282-3.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenocarcinoma / chemistry
  • Adenocarcinoma / genetics
  • Adenocarcinoma / pathology*
  • Aged
  • Cyclin-Dependent Kinase Inhibitor p16 / analysis*
  • Disease Progression
  • Disease-Free Survival
  • G1 Phase
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Genes, Retinoblastoma*
  • Genes, p16*
  • Humans
  • Loss of Heterozygosity
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Proteins / analysis*
  • Prostatic Neoplasms / chemistry
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / pathology*
  • Retinoblastoma Protein / analysis*


  • Cyclin-Dependent Kinase Inhibitor p16
  • Neoplasm Proteins
  • Retinoblastoma Protein