title: Phosphorylation of signal transducer and activator of transcription 3 (STAT3) correlates with Her-2 status, carbonic anhydrase 9 expression and prognosis in esophageal cancer.
abstract: The signal-transcriptional factor signal transducer and activator of transcription (STAT3) is overexpressed in various tumor entities and promotes tumor progression and metastasis. The tyrosine-kinase receptor Her-2 was shown to activate STAT3-expression and is overexpressed in a subtype of esophageal cancer (EC). STAT3 also regulates carbonic anhydrase IX (CAIX) expression in vivo, promoting IL-6-dependent tumor invasion.Tumor-tissue from 324 patients with EC and 45 patients with precursor lesions were analyzed for the expressions of tyrosine-705 phosphorylated STAT3 (pSTAT3). Data on Her-2-status and CAIX expression were available from previous studies. pSTAT3 was overexpressed in 40 % of adenocarcinomas (AC) and 50 % of squamous cell carcinomas of the esophagus and was associated with worse overall (OS) (p = 0.001) and disease free survival (DFS) (p = 0.001). In Barrett's mucosa without/low-grade dysplasia, pSTAT3 was expressed in 14 % compared to 27 % in patients with high-grade dysplasia (p = 0.018). A significant association between Her-2 and pSTAT3 was found in ACs (p = 0.013), showing that patients with tumors expressing both proteins have significantly worse OS (p = 0.0039) and DFS (p = 0.029). One hundred-fifty (46.3 %) cancer cases were considered as positive for CAIX expression, and a strong correlation between pSTAT3 and CAIX expression was seen (p < 0.001). pSTAT3 plays an important role in the development of AC. Expression of pSTAT3 correlates with Her-2 status and CAIX expression and is associated with tumor progression and worse outcome, offering expectantly therapeutical implications.
authors.affiliation: Department of Surgery, Cancer Comprehensive Center Vienna, University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria. sebastian.schoppmann@meduniwien.ac.at
authors.forename: Sebastian F
authors.initials: SF
authors.lastname: Schoppmann
authors.forename: Bettina
authors.initials: B
authors.lastname: Jesch
authors.forename: Julia
authors.initials: J
authors.lastname: Friedrich
authors.forename: Gerd
authors.initials: G
authors.lastname: Jomrich
authors.forename: Florian
authors.initials: F
authors.lastname: Maroske
authors.forename: Peter
authors.initials: P
authors.lastname: Birner
mesh_terms: D000368:Aged; D000951:Antigens, Neoplasm / Q000096:biosynthesis*; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000096:biosynthesis*; D018572:Disease-Free Survival; D004938:Esophageal Neoplasms / Q000175:diagnosis / Q000201:enzymology*; D005260:Female; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D011379:Prognosis; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D013997:Time Factors; D014443:Tyrosine / Q000737:chemistry
chemical_list: D000951:Antigens, Neoplasm; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases; D018719:Erb-b2 Receptor Tyrosine Kinases; D050796:STAT3 Transcription Factor; D014443:Tyrosine; C089226:CA9 protein, human