Prognostic significance of SATB1 expression in metastatic colorectal cancer: A Nordic prospective cohort study.

Abstract

707 Background: Special AT-rich sequence binding protein 1 (SATB1) is a transcription factor involved in global gene regulation. SATB1 expression has been associated with poor prognosis in numerous cancer forms, including colorectal cancer (CRC). The value of SATB1 expression in metastatic CRC (mCRC) has, however, not yet been described. The aim was to evaluate the expression and prognostic significance of SATB1 in mCRC. Methods: SATB1 expression was analysed by immunohistochemistry in tissue microarrays with tumors from a prospective cohort with 454 mCRC patients from three Nordic countries. Cox regression proportional hazards models were applied to assess the impact of SATB1 expression on overall survival (OS); in the entire cohort, and in strata per chemotherapy and mutational status. Results: Among the 454 evaluable cases, 144 (32%) were positive and 310 (68%) were negative for SATB1 expression. Positive SATB1 expression was significantly more frequent in cases with lung metastases (41% vs 29%, p = 0.018), but did not correlate with other sites of distant metastasis. SATB1 expression (positive vs negative) was not prognostic in the entire cohort. The prognostic value of SATB1 did not differ between patients receiving palliative treatment (n = 281) and untreated patients (n = 178), and did not differ in relation to type of chemotherapy. In patients with BRAF wild type tumors, SATB1 expression was significantly associated with prolonged OS, whereas the opposite was seen in BRAF mutated tumors (hazard ratio = 0.77 vs 1.60, p for interaction = 0.005). SATB1 expression was significantly associated with prolonged OS in patients with KRAS mutated tumors (hazard ratio = 0.68), but not in KRAS wild type tumors, and there was no significant prognostic interaction between SATB1 expression and KRAS status. The prognostic value of SATB1 expression did not differ by tumor location. Conclusions: The prognostic value of SATB1 expression in mCRC appears to depend on the mutational status of the tumors, in particular BRAF. The potential value of SATB1 expression as a predictive biomarker for targeted therapies merits further investigation.