Activated STAT3 as a correlate of distant metastasis in prostate cancer: a secondary analysis of Radiation Therapy Oncology Group 86-10.
OBJECTIVE
STAT3 participates in the regulation of cellular growth, survival, and oncogenesis. We evaluated the association between activated STAT3 expression and overall survival, disease-specific survival, distant metastasis, and local progression in a cohort of patients treated with either radiotherapy alone or radiotherapy plus short-term androgen blockade.


METHODS
A total of 456 assessable patients were included in the Radiation Therapy Oncology Group 86-10 trial. Of these, 62 patients had sufficient tissue for the analysis of STAT3 expression by immunohistochemistry. Nuclear staining was quantified by an image analysis system.


RESULTS
No significant difference was found in the distribution of clinical characteristics and assigned treatment between the patients available for STAT3 analysis (STAT3 cohort) and the others in the Radiation Therapy Oncology Group 86-10 trial (n = 394). Activated STAT3 correlated inversely with the development of distant metastasis (risk ratio [RR] = 0.81, P = 0.04) but not with overall survival, cause-specific survival, or local progression. Similar results were obtained when the data were dichotomized (ACIS index greater than 29%, RR = 0.41, P = 0.07). On multivariate analysis, activated STAT3 (continuous variable) was an independent predictor of distant metastasis (RR = 0.79, P = 0.04).


CONCLUSIONS
Activated STAT3 was inversely related to the development of distant metastasis in prostate cancer. This marker should be evaluated further in a larger cohort of patients.
Torres-Roca
Javier F
JF
Department of Interdisciplinary Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612, USA. Javier.Torresroca@moffitt.org
DeSilvio
Michelle
M
Mora
Linda B
LB
Khor
Li Yan
LY
Hammond
Elizabeth
E
Ahmad
Nazeel
N
Jove
Richard
R
Forman
Jeffrey
J
Lee
R Jeffrey
RJ
Sandler
Howard
H
Pollack
Alan
A
D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D003131:Combined Modality Therapy; D018450:Disease Progression; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D011467:Prostate / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D016019:Survival Analysis; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D050796:STAT3 Transcription Factor