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 pr...

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Bibliographic Details
Published in:Cancer letters 2002-11, Vol.185 (2), p.191-199
Main Authors: Jarrard, David F., Modder, Joshua, Fadden, Paul, Fu, Vivian, Sebree, Linda, Heisey, Dennis, Schwarze, Steven R., Friedl, Andreas
Format: Article
Language:English
Subjects:
Adenocarcinoma - chemistry
Adenocarcinoma - genetics
Adenocarcinoma - pathology
Aged
Arrays
Biological and medical sciences
Colleges & universities
Cyclin-Dependent Kinase Inhibitor p16 - analysis
Disease Progression
Disease-Free Survival
Dissemination
DNA methylation
Epigenetics
G1 Phase
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Genes, p16
Genes, Retinoblastoma
Humans
Loss of Heterozygosity
Male
Medical sciences
Middle Aged
Neoplasm Metastasis
Neoplasm Proteins - analysis
p16
pRb
Prostate cancer
Prostatic Neoplasms - chemistry
Prostatic Neoplasms - genetics
Prostatic Neoplasms - pathology
Retinoblastoma Protein - analysis
Senescence
Tumor cell
Tumors
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Summary: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.
ISSN:0304-3835
1872-7980
DOI:10.1016/S0304-3835(02)00282-3