演題抄録

International Session(Oral)

開催概要
開催回
第51回・2013年・京都
 

Involvement of Jak/STAT Pathway in Esophageal Cancer

演題番号 : ISO1-1

[筆頭演者]
Aysegul Ilhan-mutlu:1,4 
[共同演者]
Matthias Preusser:1,4、Sebastian Schoppmann:2,4、Peter Birner:3,4

1:Department of Oncology, Medical University of Vienna, Austria、2:Department of Surgery, Medical University of Vienna, Vienna, Austria、3:Department of Pathology, Medical University of Vienna, Austria、4:CCC- Gastroesophageal Tumor Unit, Medical University of Vienna, Austria

 

Background: Rates of esophageal cancer are increasing worldwide. Despite of multimodal treatment efforts, outcome is still poor. Janus kinase (JAK) enzymes are non-receptor tyrosine kinases mediating signal transduction in pathways involved in cell growth and survival. Signal transducer and activator of transcription 3 (STAT) protein is the main downstream effector of JAK, and we showed in a previous study the clinical relevance of STAT3 activation in esophageal cancer. Inhibitors of JAKs are available and are either already in use or under approval for treatment of myeloproliferative diseases, rheumatoid arthritis and psoriasis. In the following study, we investigated the role of the JAK1/2-STAT3 pathway in esophageal cancer. Method: The expressions of phosphorylated JAK1, JAK2 and activated STAT3 were evaluated in a large cohort of esohageal cancer patients (adenocarcinoma, n=157; squamous cell carcinoma, 129) from formalin fixed paraffin embedded tissue using immunohistochemistry. Results: Phosphorylated JAK1, STAT3 and JAK2 were overexpressed in 58%, 29 % and 42% of adenocarcinoma and 83%, 52%, 28% of squamous cell carcinoma of esophagus, respectively. JAK2 expression correlated with that of pSTAT3 (p<0.001, Chi square test), and was associated with shorter disease free (p=0.03, Cox regression) and overall survival (p=0.006, Cox regression) in multivariate analysis. Currently we are inhibiting the JAK/STAT pathway in esophageal cancer cells lines in vitro, results will be presented in detail.Discussion: The JAK/STAT signalling pathway plays a significant role in esophageal carcinoma and its inhibition might represent a novel treatment modality in this disease.

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