Loss of nuclear localized and tyrosine phosphorylated Stat5 in breast cancer predicts poor clinical outcome and increased risk of antiestrogen therapy failure. J Clin Oncol 2011 Jun 20;29(18):2448-58
Date
05/18/2011Pubmed ID
21576635Pubmed Central ID
PMC3675698DOI
10.1200/JCO.2010.30.3552Scopus ID
2-s2.0-79959309120 (requires institutional sign-in at Scopus site) 88 CitationsAbstract
PURPOSE: To investigate nuclear localized and tyrosine phosphorylated Stat5 (Nuc-pYStat5) as a marker of prognosis in node-negative breast cancer and as a predictor of response to antiestrogen therapy.
PATIENTS AND METHODS: Levels of Nuc-pYStat5 were analyzed in five archival cohorts of breast cancer by traditional diaminobenzidine-chromogen immunostaining and pathologist scoring of whole tissue sections or by immunofluorescence and automated quantitative analysis (AQUA) of tissue microarrays.
RESULTS: Nuc-pYStat5 was an independent prognostic marker as measured by cancer-specific survival (CSS) in patients with node-negative breast cancer who did not receive systemic adjuvant therapy, when adjusted for common pathology parameters in multivariate analyses both by standard chromogen detection with pathologist scoring of whole tissue sections (cohort I; n = 233) and quantitative immunofluorescence of a tissue microarray (cohort II; n = 291). Two distinct monoclonal antibodies gave concordant results. A progression array (cohort III; n = 180) revealed frequent loss of Nuc-pYStat5 in invasive carcinoma compared to normal breast epithelia or ductal carcinoma in situ, and general loss of Nuc-pYStat5 in lymph node metastases. In cohort IV (n = 221), loss of Nuc-pYStat5 was associated with increased risk of antiestrogen therapy failure as measured by univariate CSS and time to recurrence (TTR). More sensitive AQUA quantification of Nuc-pYStat5 in antiestrogen-treated patients (cohort V; n = 97) identified by multivariate analysis patients with low Nuc-pYStat5 at elevated risk for therapy failure (CSS hazard ratio [HR], 21.55; 95% CI, 5.61 to 82.77; P < .001; TTR HR, 7.30; 95% CI, 2.34 to 22.78; P = .001). CONCLUSION Nuc-pYStat5 is an independent prognostic marker in node-negative breast cancer. If confirmed in prospective studies, Nuc-pYStat5 may become a useful predictive marker of response to adjuvant hormone therapy.
Author List
Peck AR, Witkiewicz AK, Liu C, Stringer GA, Klimowicz AC, Pequignot E, Freydin B, Tran TH, Yang N, Rosenberg AL, Hooke JA, Kovatich AJ, Nevalainen MT, Shriver CD, Hyslop T, Sauter G, Rimm DL, Magliocco AM, Rui HMESH terms used to index this publication - Major topics in bold
AdultAged
Aged, 80 and over
Antineoplastic Agents, Hormonal
Breast Neoplasms
Carcinoma, Ductal, Breast
Carcinoma, Intraductal, Noninfiltrating
Cohort Studies
Disease Progression
Disease-Free Survival
Drug Resistance, Neoplasm
Estrogen Receptor Modulators
Female
Humans
Lymphatic Metastasis
Middle Aged
Neoplasm Proteins
Nuclear Proteins
Phosphorylation
Phosphotyrosine
Prognosis
Protein Processing, Post-Translational
STAT5 Transcription Factor
Survival Analysis
Treatment Failure
Tumor Suppressor Proteins
Young Adult
