The incidence, correlation with tumor-infiltrating inflammation, and prognosis of phosphorylated STAT3 expression in human gliomas

Clin Cancer Res. 2008 Dec 15;14(24):8228-35. doi: 10.1158/1078-0432.CCR-08-1329.

Abstract

Purpose: The signal transducer and activator of transcription 3 (STAT3) is frequently overexpressed in most cancers, propagates tumorigenesis, and is a key regulator of immune suppression in cancer patients. We sought to determine the incidence of phosphorylated STAT3 (p-STAT3) expression in malignant gliomas of different pathologic types, whether p-STAT3 expression is a negative prognostic factor, and whether p-STAT3 expression influences the inflammatory response within gliomas.

Methods: Using immunohistochemical analysis, we measured the incidence of p-STAT3 expression in 129 patients with gliomas of various pathologic types in a glioma tissue microarray. We categorized our results according to the total number of p-STAT3-expressing cells within the gliomas and correlated this number with the number of infiltrating T cells and T regulatory cells. We then evaluated the association between p-STAT3 expression and median survival time using univariate and multivariate analyses.

Results: We did not detect p-STAT3 expression in normal brain tissues or low-grade astrocytomas. We observed significant differences in the incidence of p-STAT3 expression between the different grades of astrocytomas and different pathologic glioma types. p-STAT3 expression was associated with the population of tumor-infiltrating immune cells but not with that of T regulatory cells. On univariate analysis, we found that p-STAT3 expression within anaplastic astrocytomas was a negative prognostic factor.

Conclusions: p-STAT3 expression is common within gliomas of both the astrocytic and oligodendroglial lineages and portends poor survival in patients with anaplastic astrocytomas. p-STAT3 expression differs significantly between gliomas of different pathologic types and grades and correlated with the degree of immune infiltration.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Brain Neoplasms / chemistry*
  • Brain Neoplasms / mortality
  • Brain Neoplasms / pathology
  • Child
  • Child, Preschool
  • Glioma / chemistry*
  • Glioma / mortality
  • Glioma / pathology
  • Humans
  • Lymphocytes, Tumor-Infiltrating / physiology*
  • Middle Aged
  • Phosphorylation
  • Prognosis
  • STAT3 Transcription Factor / analysis*
  • T-Lymphocytes, Regulatory / physiology*

Substances

  • STAT3 Transcription Factor
  • STAT3 protein, human