Phosphorylated signal transducer and activator of transcription–3 (p-STAT3) expression concordance in paired primary and metastatic colorectal cancers (mCRC): Updated analysis.

Abstract

e15137 Background: p-STAT3 is a transcription factor which is associated with poor prognosis in multiple cancers. Overexpression of p-STAT3 by immunohistochemistry (IHC) in tumors of patients with mCRC is associated with more aggressive disease and decreased survival. Concordance of p-STAT3 expression in primary and metastatic tumors was assessed to determine the temporal heterogeneity of expression and correlation with clinical outcomes. Methods: Patients with tissue available from both primary and liver metastases were identified retrospectively. Tissue microarrays (TMA) were constructed using 2 x 2mm cores. Nuclear p-STAT3 expression intensity by IHC was graded as absent, low, or high. Primary outcome was concordance of p-STAT3 expression between primary and metastatic sites. Secondary outcome was correlation of p-STAT3 expression with disease outcomes. Results: 91 patients were identified: 55% were male, median age at diagnosis was 63, 60% had left-sided disease and 81% of metastases were synchronous. Expression of p-STAT3 in primary tumors was 23% high, 47% low and absent in 30% compared to 29% high, 50% low, and 21% absent in metastases. Concordant expression was observed in 23% of patients whereas it increased in 46% and decreased in 31% from primary to metastasis. Pearson’s correlation was 0.119 indicating a weak concordance. After a median follow-up of 7 years, 50 of 91 patients died. One-year and 5-year survival rates were 92% and 44% respectively, while the median overall survival (mOS) was 4.7 years [95%CI 3.1-6.4]. No significant prognostic correlation between primary or metastatic p-STAT3 expression and mOS was found. Conclusions: There was low concordance of p-STAT3 expression in primary and metastatic tumors of patients with mCRC. Tumor staining heterogeneity due to sampling of small cores included in TMA and predominance of synchronous metastases may play a role. Further research in the use of p-STAT3 as a biomarker in patients with mCRC is needed.