Signal transducer and activator of transcription-5 activation and breast cancer prognosis.
OBJECTIVE
Transcription factor signal transducer and activator of transcription-5 (Stat5) promotes breast epithelial cell differentiation. We retrospectively analyzed whether levels of active Stat5 in breast cancer were linked to clinical outcome.


METHODS
Immunohistochemistry was used to detect active, tyrosine-phosphorylated Stat5 in paraffin-embedded breast cancer specimens from three archival tissue microarray materials A, B, and C. Material A included 19 healthy human breast tissues and a progression series of primary lymph node-negative, primary lymph node-positive, and metastatic breast cancer (n = 400). Materials B (n = 785) and C (n = 570) represented two independent arrays of unselected primary breast cancer specimens with clinical follow-up data.


RESULTS
Material A demonstrated that Stat5 activation, but not Stat5 protein expression, was gradually lost during cancer progression, with detectable activation in 100% of healthy breast specimens compared with less than 20% of node-positive breast cancers and metastases. Stat5 activation in tumors of material B was associated with favorable prognosis. This observation was confirmed and extended in material C to include both breast cancer-specific survival and disease-free survival. Stat5 activation remained an independent prognostic marker after adjusting for patient age, tumor size, histological grade, estrogen receptor, progesterone receptor, and Her2/neu status by Cox multivariate analysis (hazard ratio, 2.0; P =.029). Stat5 activation was a particularly favorable marker in the lymph node-negative breast cancer subpopulation (hazard ratio, 7.5; P =.003).


CONCLUSIONS
In our study, active Stat5 distinguishes breast cancer patients with favorable prognosis, and may be a useful marker for selection of more individualized treatment, especially in localized disease. These findings require confirmation in a large prospective study.
Nevalainen
Marja T
MT
Lombardi Comprehensive Cancer Center NRB E504, Georgetown University, 3970 Reservoir Rd NW, Washington, DC 20057-1469, USA.
Xie
Jianwu
J
Torhorst
Joachim
J
Bubendorf
Lukas
L
Haas
Philippe
P
Kononen
Juha
J
Sauter
Guido
G
Rui
Hallgeir
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D008894:Milk Proteins; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D011379:Prognosis; D050799:STAT5 Transcription Factor; D015996:Survival Rate; D015534:Trans-Activators / Q000378:metabolism*; D025521:Tumor Suppressor Proteins
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D008894:Milk Proteins; D050799:STAT5 Transcription Factor; C494092:STAT5A protein, human; D015534:Trans-Activators; D025521:Tumor Suppressor Proteins