Expression of p27Kip1 and cyclin D1 proteins is inversely correlated and is associated with poor clinical outcome in human gastric cancer

J Surg Oncol. 1999 Jul;71(3):147-54. doi: 10.1002/(sici)1096-9098(199907)71:3<147::aid-jso3>3.0.co;2-5.

Abstract

Background and objectives: p27Kip1 is an inhibitor of cyclin-dependent kinases and is speculated to be a potential prognostic indicator in numerous human cancers. We investigated expression of p27Kip1 along with cyclin D1 in gastric cancer to estimate the clinical utility of p27Kip1.

Methods: Immunohistochemical assay for p27Kip1 and cyclin D1 proteins was performed in 64 patients with primary gastric cancer. Correlation between p27Kip1 expression and clinical-biological parameters including patient survival was analyzed.

Results: p27Kip1 expression was suppressed in 40 (62.5%) of 64 gastric cancer patients and cyclin D1 was overexpressed in 22 (34.4%) out of 64. Expression of p27Kip1 was significantly reduced in poorly differentiated cancers (82.1%, 23/28; P = 0.015) and was also reduced in the tumors with high S-phase fraction (86.7%, 26/30) compared with tumors showing low S-phase fraction (41.2%, 14/34; P = 0.0002). Expression of p27Kip1 and cyclin D1 was inversely correlated (P = 0.021). In univariate analysis, extent of the disease (P < 0.001), expression of cyclin D1 (P = 0.0001), and reduced expression of p27Kip1 (P = 0. 0006), were statistically significant to predict patient's outcome, but depth of invasion (P = 0.008) and pathologic stage (P = 0.009) emerged as significant prognostic indicators in multivariate analysis.

Conclusion: Expression of p27Kip1 is closely linked with cell proliferation and differentiation of human gastric cancer. p27Kip1 seems to have potential as a prognostic marker in the management of gastric cancer patients.

MeSH terms

  • Adult
  • Aged
  • Cell Cycle Proteins*
  • Cyclin D1 / biosynthesis*
  • Cyclin-Dependent Kinase Inhibitor p27
  • Enzyme Inhibitors / metabolism*
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Microtubule-Associated Proteins / biosynthesis*
  • Middle Aged
  • Prognosis
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology
  • Survival Analysis
  • Survival Rate
  • Treatment Outcome
  • Tumor Suppressor Proteins*

Substances

  • Cell Cycle Proteins
  • Enzyme Inhibitors
  • Microtubule-Associated Proteins
  • Tumor Suppressor Proteins
  • Cyclin D1
  • Cyclin-Dependent Kinase Inhibitor p27