Table of Contents
Definition / general | Essential features | Pathophysiology | Diagrams / tables | Clinical features | Interpretation | Uses by pathologists | Prognostic factors | Microscopic (histologic) images | Positive staining - normal | Positive staining - disease | Negative staining | Board review style question #1 | Board review style answer #1Cite this page: De Michele S, Remotti HE. Special AT-rich sequence-binding protein 2 (SATB2). PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stainsSATB2.html. Accessed January 15th, 2025.
Definition / general
- First identified in 2002 and characterized as a gene involved in cleft palate defects (Arch Pathol Lab Med 2017;141:1428)
- Part of the matrix attachment region binding transcription factor family, which consists of transcription factors binding to adenine and thymine (AT) rich regions in the nuclear matrix, capable of altering the chromatin structure (Arch Pathol Lab Med 2017;141:1428)
Essential features
- Nuclear marker normally expressed by epithelium of the lower gastrointestinal tract, brain, nongerminal center lymphoid cells, ductal epithelium of the testis and epididymis
- High sensitivity and specificity for colorectal and appendiceal neoplasms; also can help diagnose osteosarcoma
- Useful in an immunostaining panel of tumor of unknown primary to rule in colorectal metastasis (Am J Clin Pathol 2021;155:124)
- Can be expressed in a subset of upper gastrointestinal adenocarcinomas; is rarely expressed in lung adenocarcinomas and pancreatobiliary neoplasms (Am J Clin Pathol 2021;155:124)
- In contrast to CDX2, SATB2 positivity is rare in mucinous and enteric pulmonary adenocarcinomas
Pathophysiology
- Critical role in neocortical and craniofacial development (Histopathology 2020;76:251)
- Role in osteoblast differentiation via interactions with transcriptional regulator RUNX2 and a microRNA network (Arch Pathol Lab Med 2017;141:1428)
Diagrams / tables
Clinical features
- Alterations of SATB2 gene (including intragenic duplication, deletions and point mutations in 2q32-q33) have been associated with SATB2 associated syndrome (SAS) (Am J Med Genet A 2014;164A:3083)
- Phenotype is characterized by intellectual disability and craniofacial abnormalities, including cleft palate, dysmorphic features and dental abnormalities (Am J Med Genet A 2015;167A:1026)
Interpretation
- Nuclear stain
Uses by pathologists
- Differentiate colorectal carcinomas (SATB2+) from many other metastatic adenocarcinomas
- Differentiate colorectal metastasis (SATB2+) from primary pulmonary adenocarcinoma of mucinous or enteric type (SATB2- but often CDX2+)
- Differentiate metastatic colorectal adenocarcinomas (SATB2+) from pancreatobiliary neoplasms (SATB2-) (Am J Clin Pathol 2021;155:124)
- Differentiate ovarian metastases of colorectal and appendiceal origin (SATB2+) from primary ovarian tumors of mucinous or endometrioid type (SATB2-) (Am J Surg Pathol 2016;40:419)
- Differentiate osteosarcomas (SATB2+) from their malignant bone tumor mimickers, such as Ewing sarcomas (SATB2-) (Pathol Res Pract 2016;212:811)
- As part of a panel in tumors of unknown origin (Pathol Res Pract 2016;212:811)
Prognostic factors
- Higher SATB2 expression is associated with better prognosis and response to chemotherapy in metastatic colorectal carcinomas (Acta Oncol 2020;59:284)
- Low SATB2 expression and mutated BRAF are associated with particularly poor prognosis (Acta Oncol 2020;59:284)
Microscopic (histologic) images
Contributed by Simona De Michele, M.D., Sepideh Besharati, M.D. and Anjali Saqi, M.D.
Positive staining - normal
- Epithelium of the lower gastrointestinal tract (including appendix, colon and rectum) (Arch Pathol Lab Med 2017;141:1428)
- Brain (including in the cerebral cortex and hippocampus) (Arch Pathol Lab Med 2017;141:1428)
- Nongerminal center lymphoid cells (Arch Pathol Lab Med 2017;141:1428)
- Ductal epithelium of the testis and epididymis (Arch Pathol Lab Med 2017;141:1428)
Positive staining - disease
- Lower gastrointestinal tract: adenocarcinomas, well differentiated neuroendocrine tumors, medullary carcinomas (Am J Surg Pathol 2011;35:937, Histopathology 2020;76:251, Arch Pathol Lab Med 2014;138:1015)
- Subset of small intestinal adenocarcinoma (up to 50% SATB2+) (Am J Clin Pathol 2021;155:124, J Clin Pathol 2016;69:1046, Arch Pathol Lab Med 2014;138:1015)
- Neoplasms with osteoblastic differentiation (osteosarcomas and several benign bone tumors) (Histopathology 2013;63:36)
- Some soft tissue malignancies (including liposarcomas) (Arch Pathol Lab Med 2017;141:1428)
- Merkel cell carcinoma (79% SATB2+) (Histopathology 2020;76:251)
Negative staining
- Pancreatic adenocarcinomas and well differentiated neuroendocrine tumors (Am J Clin Pathol 2021;155:124, Histopathology 2020;76:251)
- Ampullary adenocarcinomas (Am J Clin Pathol 2021;155:124, J Transl Med 2014;12:289)
- Cholangiocarcinomas (Am J Clin Pathol 2021;155:124)
- Gastric adenocarcinoma (up to 17% can be SATB2+) and well differentiated neuroendocrine tumors (Am J Clin Pathol 2021;155:124, Histopathology 2020;76:251)
- Small intestinal well differentiated neuroendocrine tumors (Histopathology 2020;76:251)
- Pulmonary adenocarcinomas (including mucinous and enteric variant) and well differentiated neuroendocrine tumors (Am J Clin Pathol 2021;155:124, Hum Pathol 2017;64:179, Histopathology 2020;76:251)
- Pulmonary (up to 10% SATB2+) and extrapulmonary poorly differentiated neuroendocrine carcinomas (up to 35% can be SATB2+) (Histopathology 2020;76:251)
- Ovarian cancer (Am J Surg Pathol 2016;40:419)
- Breast cancer (Appl Immunohistochem Mol Morphol 2020;28:e53)
- Invasive urothelial carcinoma (up to 23% SATB2+) (Arch Pathol Lab Med 2014;138:1015)
Board review style question #1
Board review style answer #1