Phosphorylation of signal transducer and activator of transcription 3 (STAT3) correlates with Her-2 status, carbonic anhydrase 9 expression and prognosis in esophageal cancer.

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.