Abstract 5458: Individual and combined activities of STAT1 and STAT3 have prognostic relevance for the progression of colorectal carcinoma.

Abstract Aberrant activities of JAK/STAT signalling pathways have been implicated in the development and spread of various cancer entities, among them colorectal carcinoma (CRC). By immunohistochemical analysis of a tissue microarray covering more than 400 CRC biopsies from patients with full clinical documentation, the expression and activity status of STAT1 and STAT3 was determined. Results were correlated with clinical information. A significant association of high STAT1 activity (as indicated by nuclear location) with longer patient overall survival was observed. Unexpectedly, strong STAT3 expression in surgical specimens could be clearly correlated with an increase in median overall survival by about 30 months. Interestingly, combined consideration of STAT1/3 expression and activity levels in CRC specimens revealed patterns that match the clinical outcome with statistical significance. For instance, tumors with concomitant absence of STAT1 and STAT3 have a worse prognosis, while high STAT1 activity along with low STAT3 activity proved associated with longer patient survival. To address the signal transduction background of these findings, STAT1/3 expression was experimentally modified in CRC cell lines and effects on the growth of xenograft tumors were studied. Mimicking STAT1/3 patterns from patient biopsies in xenografts resulted in alterations in tumor growth well corresponding to clinical data. From these experiments we draw the conclusions that the ratio of nuclear STAT1/STAT3 is a determinant of colon carcinoma progression. Supported by: Deutsche Krebshilfe, IZKF Jena, European Regional Development Fund ERDF Citation Format: Claire Gordziel, Harini Nivarthi, Thomas Knösel, Helmut Dolznig, Richard Moriggl, Karlheinz Friedrich. Individual and combined activities of STAT1 and STAT3 have prognostic relevance for the progression of colorectal carcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5458. doi:10.1158/1538-7445.AM2013-5458