Tissue microarray analysis of signal transducers and activators of transcription 3 (Stat3) and phospho-Stat3 (Tyr705) in node-negative breast cancer shows nuclear localization is associated with a better prognosis.
OBJECTIVE
Although a high frequency of tumors contain constitutively activated signal transducers and activators of transcription 3 (Stat3), its relationship to breast cancer and patient survival has not been determined in a large retrospective study of node-negative tumors. To further elucidate the role of Stat3 in breast cancers, the expression patterns of Stat3 and Phospho-tyrosine residue 705 (Tyr705) Stat3 were correlated with survival outcome and clinicopathological parameters in a large cohort of node-negative breast cancer tumors.


METHODS
Immunohistochemical analysis of Stat3 and Phospho-Stat3 was performed on a breast cancer tissue microarray of 346 node-negative breast cancer specimens. These results were correlated with overall survival and other clinicopathological data.


RESULTS
Positive Stat3 cytoplasmic expression was seen in 69.2% of tumors, and positive Phospho-Stat3 (Tyr705) cytoplasmic expression was seen in 19.6% of tumors. Neither cytoplasmic expression showed significant association with survival or other clinical parameters. However, 23.1% of tumors had positive Stat3 nuclear expression, and those patients had a significantly improved short-term survival (P = 0.0332) at 5 years of follow-up. Upon analysis of positive Phospho-Stat3 (Tyr705) nuclear expression, seen in 43.5% of tumors, positive tumors had a significantly improved survival at both short-term 5-year survival (P = 0.0054) and long-term 20-year (P = 0.0376) survival analysis. Additionally, positive Phospho-Stat3 (Tyr705) nuclear expression is an independent prognostic marker of better overall survival node-negative breast cancer by multivariate analyses that included the variables of nuclear grade, Ki-67, estrogen receptor staining, progesterone receptor staining, Her2 staining, age, and tumor size.


CONCLUSIONS
These findings support a role for Stat3 and Phospho-Stat3 (Tyr705) overexpression in node-negative breast cancer and provide initial evidence that Phospho-Stat3 (Tyr705) may be a marker for improved overall survival independent of other prognostic markers.
Dolled-Filhart
Marisa
M
Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Camp
Robert L
RL
Kowalski
Diane P
DP
Smith
Bradley L
BL
Rimm
David L
DL
D000209:Acute-Phase Proteins / Q000032:analysis; D015415:Biomarkers / Q000032:analysis; D001943:Breast Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D015999:Multivariate Analysis; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000032:analysis*; D011379:Prognosis; D016016:Proportional Hazards Models; D050796:STAT3 Transcription Factor; D016019:Survival Analysis; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism*
D000209:Acute-Phase Proteins; D015415:Biomarkers; D004268:DNA-Binding Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D015534:Trans-Activators; D019000:Phosphotyrosine