The prognostic significance of altered cyclin-dependent kinase inhibitors in human cancer

Annu Rev Med. 1999;50:401-23. doi: 10.1146/annurev.med.50.1.401.

Abstract

Progression through the cell cycle is governed by cyclin-dependent kinases (cdks), whose activity is inhibited by the cdk inhibitors. Cyclins, cdks, and cdk inhibitors are frequently deregulated in cancers. This chapter reviews the prognostic significance of alterations in cdk inhibitors. Loss of p27 protein provides independent prognostic information in breast, prostate, colon, and gastric carcinomas, and immunohistochemical (IHC) staining for p27 may eventually become part of routine histopathologic processing of cancers. Loss of IHC staining for p21 may be prognostic in certain cancers but conflicting results are reported in breast cancer. Reports on homozygous deletion of p16 and p15 genes suggest the value of larger, prospective studies with standardized treatment protocols to definitively establish the prognostic utility of p15/p16 deletions in acute leukemias. Larger trials and the development of a consensus on methods for deletion analysis, IHC staining, and tumor scoring will be needed to move these molecular assays from bench to bedside.

Publication types

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

MeSH terms

  • Breast Neoplasms / pathology
  • Carcinoma / pathology
  • Carrier Proteins / genetics
  • Cell Cycle
  • Cell Cycle Proteins*
  • Colonic Neoplasms / pathology
  • Coloring Agents
  • Cyclin-Dependent Kinase Inhibitor p15
  • Cyclin-Dependent Kinase Inhibitor p16*
  • Cyclin-Dependent Kinase Inhibitor p27
  • Cyclin-Dependent Kinases / antagonists & inhibitors*
  • Cyclins / analysis
  • Enzyme Inhibitors / analysis*
  • Female
  • Gene Deletion
  • Genes, Tumor Suppressor / genetics
  • Genes, p16 / genetics
  • Homozygote
  • Humans
  • Immunohistochemistry
  • Leukemia / genetics
  • Male
  • Microtubule-Associated Proteins / analysis
  • Neoplasms / pathology*
  • Prognosis
  • Prospective Studies
  • Prostatic Neoplasms / pathology
  • Stomach Neoplasms / pathology
  • Tumor Suppressor Proteins*

Substances

  • CDKN2B protein, human
  • Carrier Proteins
  • Cell Cycle Proteins
  • Coloring Agents
  • Cyclin-Dependent Kinase Inhibitor p15
  • Cyclin-Dependent Kinase Inhibitor p16
  • Cyclins
  • Enzyme Inhibitors
  • Microtubule-Associated Proteins
  • Tumor Suppressor Proteins
  • Cyclin-Dependent Kinase Inhibitor p27
  • Cyclin-Dependent Kinases