Reduced expression of cell-cycle regulator p27(Kip1) correlates with a shortened survival in non-small cell lung cancer

Lung Cancer. 2001 Oct;34(1):83-90. doi: 10.1016/s0169-5002(01)00216-1.

Abstract

Background: The cell cycle progression is governed by a family of cyclin-dependent kinases, which are regulated by associated cyclins and by phosphorylation. p27, a cyclin-dependent kinase inhibitor, regulates the progression from G1 into the S phase by binding and inhibiting cyclin/cdks. Although p27 mutations in human tumors are extremely rare, a reduced expression of p27 might to lead to a progression of cancer cells.

Methods: We examined tissues that had been surgically excised from 161 unselected Japanese patients with non-small cell lung cancer, and investigated the p27 protein expression by immunohistochemistry.

Results: A reduced expression of the p27 protein was found in 63 cases (39.0%). Statistical correlation was found between the reduced p27 expression and advanced stage, although no correlation was found between the level of p27 expression and the gender, T factor, N factor or histological differentiation. The 5-year survival rate in the reduced group was 35.4%, which was statistically poorer than the 63.2% rate in the normal group (P=0.0016), in patients with complete resection. In a multivariate analysis, the level of p27 expression was found to be an independent prognostic indicator.

Conclusions: We demonstrated the expression of p27 protein to be a biological prognostic indicator which can indicate the subsets of patients with either a good or poor prognosis, in patients who underwent surgical resection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / biosynthesis*
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cell Cycle Proteins / analysis
  • Cell Cycle Proteins / biosynthesis*
  • Cyclin-Dependent Kinase Inhibitor p27
  • Enzyme Inhibitors / analysis*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunohistochemistry
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology*
  • Male
  • Middle Aged
  • Prognosis
  • Retrospective Studies
  • Survival Analysis
  • Tumor Suppressor Proteins / analysis
  • Tumor Suppressor Proteins / biosynthesis*

Substances

  • Biomarkers, Tumor
  • Cell Cycle Proteins
  • Enzyme Inhibitors
  • Tumor Suppressor Proteins
  • Cyclin-Dependent Kinase Inhibitor p27