SATB2 is a nuclear matrix attachment region-binding transcription factor with developmental role in craniofacial, neural, and osteoblastic differentiation. Several publications have documented SATB2 expression in the epithelium of the lower gastrointestinal tract (appendix, colon, and rectum). SATB2 expression is also seen in developing cortical and spinal cord neurons, osteoblasts, lymphocytes, epithelial cells of renal convoluted tubules, neurons in brain and germ cells in testis. 


IHC for SATB2 can be used as a marker to determine the origin of a cancer of unknown primary site (CUP). Publications have reported SATB2 in combination with CDX2 to be highly valuable to identify colorectal carcinomas with a reported analytical sensitivity typically in the range of 85-95%. Upper gastrointestinal carcinomas and pancreatic ductal carcinomas are typically negative or only rarely positive (usually <5%).  SATB2 can also be useful in the differentiation of ovarian carcinoma from colorectal carcinoma. In the literature <5% of ovarian carcinomas including the mucinous subtype have been reported to be SATB2 positive.  In many publications, IHC for SATB2 has shown a high analytical sensitivity (80-100%) for appendiceal and rectal well differentiated neuroendocrine tumours (WDNET), whereas other WDNETs e.g. from stomach, duodenum, pancreas, lung and thyroid typically will be negative or only show a weak and focal positivity (0-15%).


At present appendix/colon, tonsil and testis are suggested as recommended positive and negative tissue controls for SATB2. In appendix/colon, protocols must be calibrated to provide a moderate to strong, distinct nuclear staining reaction in virtually all columnar epithelial cells and an at least a weak to moderate nuclear staining reaction in dispersed ganglion cells of nerve plexus. In tonsil scattered interfollicular lymphocytes will be demonstrated, whereas the vast majority of lymphocytes are negative (reaction pattern in lymphoid cells might depend on antibody clone applied – see NordiQC run 58, SATB2 ). In testis dispersed germ cells must show an least weak to moderate nuclear staining reaction. No staining reaction should be seen in endothelial and smooth muscle cells.  

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