123P - Signal transducer and activator of transcription–3 (STAT3) expression concordance in paired primary and metastatic colorectal cancers (mCRC)

Date 10 October 2016
Event ESMO 2016 Congress
Session Poster display
Topics Colon Cancer
Rectal Cancer
Translational Research
Presenter Daniel Yokom
Citation Annals of Oncology (2016) 27 (6): 15-42. 10.1093/annonc/mdw363
Authors D. Yokom1, S. Sud2, H. Marginean2, T. Asmis2, D.J. Jonker3, G. Martel4, A. Gown5, M. Daneshmand6, E..C. Marginean6, R. Goodwin3
  • 1Division Of Medical Oncology, Princess Margaret Hospital, M5T 2M9 - Toronto/CA
  • 2Division Of Medical Oncology, The Ottawa Hospital Regional Cancer Centre, K1H 8L6 - Ottawa/CA
  • 3Division Of Medical Oncology, The Ottawa Hospital Regional Cancer Centre, Ottawa/CA
  • 4Department Of General Surgery, The Ottawa Hospital Regional Cancer Centre, Ottawa/CA
  • 5Department Of Pathology, PhenoPath, PLLC, Seattle/US
  • 6Department Of Pathology, The Ottawa Hospital Regional Cancer Centre, Ottawa/CA

Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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

Funding

The Ottawa Hospital Department of Medicine

Disclosure

All authors have declared no conflicts of interest.