title: Constitutive STAT5 activation correlates with better survival in cervical cancer patients treated with radiation therapy.
abstract: OBJECTIVE
  Constitutively activated signal transducers and activators of transcription (STAT) factors, in particular STAT1, STAT3, and STAT5, have been detected in a wide variety of human primary tumors and have been demonstrated to directly contribute to oncogenesis. However, the expression pattern of these STATs in cervical carcinoma is still unknown, as is whether or not they have prognostic significance. This study investigated the expression patterns of STAT1, STAT3, and STAT5 in cervical cancer and their associations with clinical outcomes in patients treated with radical radiation therapy.
  
  
  METHODS
  A total of 165 consecutive patients with International Federation of Gynecology and Obstetrics (FIGO) Stages IB to IVA cervical cancer underwent radical radiation therapy, including external beam and/or high-dose-rate brachytherapy between 1989 and 2002. Immunohistochemical studies of their formalin-fixed, paraffin-embedded tissues were performed. Univariate and multivariate analyses were performed to identify and to evaluate the effects of these factors affecting patient survival.
  
  
  RESULTS
  Constitutive activations of STAT1, STAT3, and STAT5 were observed in 11%, 22%, and 61% of the participants, respectively. While STAT5 activation was associated with significantly better metastasis-free survival (p < 0.01) and overall survival (p = 0.04), STAT1 and STAT3 activation were not. Multivariate analyses showed that STAT5 activation, bulky tumor (≥ 4 cm), advanced stage (FIGO Stages III and IV), and brachytherapy (yes vs. no) were independent prognostic factors for cause-specific overall survival. None of the STATs was associated with local relapse. STAT5 activation (odds ratio = 0.29, 95% confidence interval = 0.13-0.63) and advanced stage (odds ratio = 2.54; 95% confidence interval = 1.03-6.26) were independent predictors of distant metastasis.
  
  
  CONCLUSIONS
  This is the first report to provide the overall expression patterns and prognostic significance of specific STATs in cervical carcinoma. Our results indicate that constitutive STAT5 activation correlates with better metastasis-free survival and overall survival in cervical cancer patients who have received radiation therapy.
authors.affiliation: Department of Radiation Oncology, National Cheng Kung University, Medical College and Hospital, Tainan, Taiwan.
authors.forename: Helen H W
authors.initials: HH
authors.lastname: Chen
authors.forename: Cheng-Yang
authors.initials: CY
authors.lastname: Chou
authors.forename: Yuan-Hua
authors.initials: YH
authors.lastname: Wu
authors.forename: Wei-Ting
authors.initials: WT
authors.lastname: Hsueh
authors.forename: Chiung-Hui
authors.initials: CH
authors.lastname: Hsu
authors.forename: How-Ran
authors.initials: HR
authors.lastname: Guo
authors.forename: Wen-Ying
authors.initials: WY
authors.lastname: Lee
authors.forename: Wu-Chou
authors.initials: WC
authors.lastname: Su
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D001918:Brachytherapy / Q000401:mortality; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy / Q000556:secondary; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D050799:STAT5 Transcription Factor / Q000378:metabolism*; D047368:Tumor Burden; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy
chemical_list: D009363:Neoplasm Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; C494092:STAT5A protein, human; D025521:Tumor Suppressor Proteins