SATB2 (Special AT-rich sequence-binding protein 2) has recently been shown to be a specific biomarker of colorectal cancer (CRC). The aim of this study was to investigate the diagnostic potential of SATB2 as a means of detecting a CRC origin for liver metastases. SATB2 expression was examined in a resection cohort of 101 CRC and 273 non-CRC adenocarcinoma samples using immunohistochemistry (IHC). The diagnostic accuracy of CRC origins of livermetastases based on SATB2 and a three marker panel of SATB2, CK20 and CDX2 was evaluated using an independent cohort of 192 liver biopsies. IHC showed 97 of the 101 (96.0%) primary CRC sampleswere SATB2 positive, compared to only 6 of the 273 (2.1%) samples of other cancer types. The sensitivity, specificity and AUC values of SATB2 expression in resection sampleswere 97%, 97.1% and 0.977, respectively. Meanwhile, for the liver biopsy samples, the sensitivity, specificity and AUC values of a CRC liver metastases was 92.2%, 97.8% and 0.948 for SATB2, 95.1%, 91.0% and 0.959 for CK20, and 100%, 85.4% and 0.976 for CDX2, respectively. Further analysis demonstrated that all three-marker positivity was detected in 92/103 (89.3%) CRC and 2/89 (2.2%) non-CRC livermetastases sampled by biopsy. Our findings suggest that SATB2, asmeasured by IHC, could serve as a promising diagnostic biomarker of CRC metastases. Combining evaluation of SATB2 with CK20 and CDX2 to form a three marker panel further improved the detection of metastatic CRCs in liver biopsy tissues. (c) 2018 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license