e14054 Background: Cancer-associated inflammation has recently been identified as a key determinant of disease progression and survival in colorectal cancer(CRC). The signal transducer and activator of transcription 3(STAT3) pathway is central to the inflammatory response, and has been implicated in cancer development and progression. This study aimed to evaluate tissue expression of cytoplasmic and nuclear STAT3 expression in CRC and its association with clinicopathological variables and survival. Methods: Patients were identified from a prospectively maintained CRC database. Using immunohistochemistry on a tissue microarray, cytoplasmic and nuclear expression of phosphorylated STAT3 (p-STAT3) at both the tyrosine 705(tyr705) and serine 727(ser727) phosphorylation sites was assessed using the weighted histoscore. Associations between p-STAT3 expression and clinicopathological factors and survival were examined. Results: In 273 patients, cytoplasmic and nuclear p-STAT3 expression was examined and considered positive if staining was observed in more than 15% of tumour cells. When colonic and rectal tumours were considered together, cytoplasmic and nuclear p-STAT3 expression at both phosphorylation sites (tyr705 and ser727) showed no significant relationship with clinicopathological variables. Similarly, when colonic tumours were considered alone, cytoplasmic and nuclear p-STAT3 expression showed no association with clinicopathological factors. In rectal cancer, although cytoplasmic p-STAT3 was not significantly associated with survival, nuclear p-STAT3 expression was associated with improved survival(tyr705 p=0.007, ser727 p=0.098). Similar to the colon cancer group, rectal cancer nuclear p-STAT3 expression showed no correlation with clinicopathological variables. Conclusions: Tumour nuclear p-STAT3 expression and its association with outcome appears to depend on tumour site with improved survival associated with nuclear p-STAT3(tyr705) expression in rectal but not colon cancer. The basis of this observation is not clear and further assessment of the role of p-STAT3 in the tumour microenvironment is required.