SATB2 (special AT-rich sequence binding 2) is a 733-amino acid human DNA-binding protein involved in transcriptional regulation and chromatin remodeling (1,2). SATB2 protein expression in normal human tissue was found in the epithelium of the lower gastrointestinal tract (including appendix, colon, and rectum), as well as specific neurons (in the cerebral cortex and hippocampus), non–germinal center lymphoid cells, and the ductal epithelium of the testis and epididymis (3). In cancer tissues, SATB2 was shown to be almost exclusively expressed in colorectal carcinoma (3). This observation was followed by validation using colorectal cancer tissue from 9 different research cohorts (1558 localized and 252 metastatic colorectal adenocarcinoma). Using SATB2 as a solitary marker, SATB2 showed positive immunostaining in 92.4% (110 of 119) of stage I, 91.4% (402 of 440) of stage II, and 83.7% (431 of 515) of stage III/IV colorectal adenocarcinomas. The expression of SATB2 was analyzed in a prospective study of 840 cases in which CK20 was being used to reach a final diagnosis (4). As a solitary marker, SATB2 had a 93% sensitivity and 77% specificity in diagnosing colorectal carcinoma, but when used as a marker in combination with CK20 positivity and CK7 negativity the sensitivity was 83% and the specificity was 100% in determining colorectal origin (4). SATB2 may be useful in the common differentials of distinguishing adenocarcinomas of colorectal origin from those of gastric and pancreatic origin. SATB2 expression was analyzed in 1941 malignancy cases using tissue microarrays, and shown to be highly expressed in colorectal adenocarcinoma (96.8%; 121 of 125), with low expression in gastric adenocarcinoma (0%; 0 of 20) and pancreatic adenocarcinoma (4.2%; 4 of 95) (5). Additional studies have verified that SATB2 could serve as a clinically useful diagnostic marker for colorectal carcinomas, especially if used in a panel approach (5-8).
1. FitzPatrick DR, et al . Identification of SATB2 as the cleft palate gene on 2q32-q33. Hum Mol Genet 2003;12:2491-2501.
2. Szemes M, et al. Isolation and characterization of SATB2, a novel ATrich DNA binding protein expressed in development- and cell-specific manner in the rat brain. Neurochem Res. 2006 Feb;31(2):237-46.
3. Magnusson K, et al . SATB2 in combination with cytokeratin 20 identifies over 95% of all colorectal carcinomas. Am J Surg Pathol. 2011;35:937–48.
4. Dragomir A, et al. The role of SATB2 as a diagnostic marker for tumors of colorectal origin: results of a pathology based clinical prospective study. Am J Clin Pathol. 2014;141:630–8.
5. Lin F, et al . Cadherin-17 and SATB2 are sensitive and specific immunomarkers for medullary carcinoma of the large intestine. Arch Pathol Lab Med. 2014;138:1015–26.
6. Moh M, et al. SATB2 expression distinguishes ovarian metastases of colorectal and appendiceal origin from primary ovarian tumors of mucinous or endometrioid type. Am J Surg Pathol. 2016;40(3):419–32.
7. Berg KB, Schaeffer DF. SATB2 as an Immunohistochemical Marker for Colorectal Adenocarcinoma: A Concise Review of Benefits and Pitfalls. Arch Pathol Lab Med 2017;141:1428-33.
8. Zhang YJ, et al . SATB2 is a Promising Biomarker for Identifying a Colorectal Origin for Liver Metastatic Adenocarcinomas. EBioMedicine. 2018 Feb;28:62-9.