The incidence, correlation with tumor-infiltrating inflammation, and prognosis of phosphorylated STAT3 expression in human gliomas.
OBJECTIVE
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.
Abou-Ghazal
Mohamed
M
Department of Neurosurgery, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Yang
David S
DS
Qiao
Wei
W
Reina-Ortiz
Chantal
C
Wei
Jun
J
Kong
Ling-Yuan
LY
Fuller
Gregory N
GN
Hiraoka
Nobuyoshi
N
Priebe
Waldemar
W
Sawaya
Raymond
R
Heimberger
Amy B
AB
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005910:Glioma / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000502:physiology*; D008875:Middle Aged; D010766:Phosphorylation; D011379:Prognosis; D050796:STAT3 Transcription Factor / Q000032:analysis*; D050378:T-Lymphocytes, Regulatory / Q000502:physiology*
D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human