STAT3 is a constitutively activated transcription factor in several cancers. In patients with mCRC overexpression of STAT3 is associated with worse survival. To determine if STAT3 is a potential target for therapy and to evaluate expression through metastatic progression in mCRC the concordance of expression in primary and metastatic tumors was assessed.
Patients treated at the Ottawa Hospital from 2001-2012 were retrospectively identified and included if tumor tissue was available from both the primary and a metastasis. Tissue microarrays were constructed using 2 x 2mm cores for each tumor. Nuclear phosphorylated STAT3 expression intensity by immunohistochemistry was evaluated by 2 independent pathologists as 0 (absent), 1-2 (low), or 3 (high). The primary outcome was concordance of STAT3 expression between primary and metastatic sites. Secondary outcomes included correlation of STAT3 expression with demographic and disease characteristics as well as clinical outcomes.
Among 38 patients identified 52% were male, median age at diagnosis was 61, and 36% of metastases were synchronous. Expression of STAT3 in primary tumors was 5% high, 42% low and absent in 53% compared to 16% high, 47% low, and 37% absent in metastatic samples. Expression between paired primary and metastatic samples was concordant in 33% of patients whereas it increased in 21% and decreased in 45%. A weak correlation was observed between primary and metastatic STAT3 expression (Pearson's correlation 0.1). After a median follow-up of 13.1 years, 30 of 35 patients included in the survival analysis died. Median survival was 4.6 years. Higher STAT3 expression in primary tumors showed a trend towards worse survival (HR 1.7, 95% CI 0.81-3.64, p = 0.1), while there was no prognostic correlation of STAT3 expression in metastases.
In patients with mCRC there was low concordance of STAT3 expression in primary and metastatic tumors. STAT3 expression in the primary, but not the metastatic site, was related to survival, indicating that the prognostic value of STAT3 depended on tumor sampling. These results have important implications for further research in the use of STAT3 as a biomarker in patients with mCRC.
Clinical trial identification
Legal entity responsible for the study
Ottawa Hospital Research Institute
The Ottawa Hospital Department of Medicine
All authors have declared no conflicts of interest.