Expression of phosphorylated Stat5 predicts expression of cyclin D1 and correlates with poor prognosis of colonic adenocarcinoma

Int J Colorectal Dis. 2011 Jan;26(1):29-35. doi: 10.1007/s00384-010-1090-7. Epub 2010 Nov 16.

Abstract

Purpose: Constitutive activation of signal transducer and activator of transcription-5 (Stat5) was recently found to be associated with tumor progression through stimulating cell proliferation and preventing apoptosis. However, it is not clear how activated Stat5 is expressed in colon cancer. We aimed to investigate the correlation between phosphorylated Stat5 (p-Stat5) expression and cell cycle regulators (cyclin D1) expression in colonic adenocarcinoma and the relationship between expression of these two proteins and various clinicopathological parameters, including overall survival.

Methods: P-Stat5 and cyclin D1 expression were determined by immunohistochemical staining from 169 cases of resected colonic adenocarcinoma specimens.

Results: P-Stat5 expression correlated with cyclin D1 expression (r = 0.250, P = 0.001). P-Stat5-positive staining was associated with the depth of tumor invasion (P = 0.002). Univariate survival analysis showed that lymph node metastasis, distant metastasis, TNM stage (all P < 0.0001), T stage (P = 0.024), p-Stat5-positive expression (P = 0.002), and cyclin D1-positive expression (P = 0.039) were associated with shorter survival in patients with colonic adenocarcinoma. Multivariate survival analysis showed that only distant metastasis (P < 0.001; hazard ratio [HR] = 4.96), TNM stage (P < 0.001; HR = 9.80), and p-Stat5 overexpression (P = 0.020; HR = 1.84) were independent predictors of poor prognosis.

Conclusions: Our findings provide the first evidence that p-Stat5 may play an important role in cyclin D1 overexpression and contribute to colonic adenocarcinoma progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / diagnosis*
  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Colonic Neoplasms / diagnosis*
  • Colonic Neoplasms / metabolism*
  • Colonic Neoplasms / pathology
  • Cyclin D1 / metabolism*
  • Female
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Phosphorylation
  • Prognosis
  • STAT5 Transcription Factor / metabolism*
  • Tumor Suppressor Proteins / metabolism*

Substances

  • CCND1 protein, human
  • STAT5 Transcription Factor
  • STAT5A protein, human
  • Tumor Suppressor Proteins
  • Cyclin D1