Wnt/beta-Catenin pathway in human glioma: expression pattern and clinical/prognostic correlations

Clin Exp Med. 2011 Jun;11(2):105-12. doi: 10.1007/s10238-010-0110-9. Epub 2010 Aug 31.

Abstract

Gliomas are the most common primary intracranial tumors. Understanding the molecular basis of gliomas' progression is required to develop more effective therapies. The Wnt/β-catenin signaling cascade is an important signal transduction pathway in human cancers. Although, overactivation of this pathway is a hallmark of several forms of cancer, little is known about its role in human gliomas. Here, we aimed to determine the clinical significance of Wnt/β-catenin pathway components in gliomas. Immunohistochemical staining was performed to detect the expression patterns of Wnt1, β-catenin and Cyclin D1 in the biopsies from 96 patients with primary gliomas. Kaplan-Meier survival and Cox regression analyses were performed to evaluate the prognosis of patients. Cytoplasmic staining pattern of Wnt1, membranous, cytoplasmic and nuclear accumulation of β-catenin, and nuclear localization of Cyclin D1 were demonstrated by immunohistochemical staining. The Wnt1 expression significantly correlated with the expression of Cyclin D1 (P < 0.0001). The ratio of tumors with a cytoplasmic-nuclear pattern or a cytoplasmic pattern of β-catenin was significantly higher in Wnt1-positive (P < 0.01) and Cyclin D1-positive (P < 0.01) tumors than in Wnt1-negative and Cyclin D1-negative tumors, respectively. The protein expression levels of Wnt1, β-catenin and Cyclin D1 were all positively correlated with the Karnofsky performance scale (KPS) score and World Health Organization (WHO) grades of patients with gliomas. Furthermore, Wnt1, cytoplasmic-nuclear β-catenin and Cyclin D1 status were all the independent prognostic factors for glioma patients (P = 0.01, 0.007 and 0.005, respectively). These results provide convincing evidence that the Wnt/β-catenin pathway correlated closely with the progression of gliomas and might be a novel prognostic marker for this neoplasm.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biopsy
  • Cyclin D1 / biosynthesis
  • Gene Expression Profiling*
  • Glioma / diagnosis*
  • Glioma / pathology
  • Glioma / physiopathology*
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Prognosis
  • Severity of Illness Index
  • Wnt1 Protein / biosynthesis*
  • beta Catenin / biosynthesis*

Substances

  • CCND1 protein, human
  • CTNNB1 protein, human
  • Wnt1 Protein
  • beta Catenin
  • Cyclin D1