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

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.

• Authors: Mohamed Abou-Ghazal, David S Yang, Wei Qiao, Chantal Reina-Ortiz, Jun Wei, Ling-Yuan Kong, Gregory N Fuller, Nobuyoshi Hiraoka, Waldemar Priebe, Raymond Sawaya, Amy B Heimberger
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 14 Issue 24 Pg. 8228-35 (Dec 15 2008) ISSN: 1078-0432 [Print] United States
• PMID: 19088040 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• STAT3 Transcription Factor
• STAT3 protein, human

Topics

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