SATB2 in neuroendocrine neoplasms: strong expression is restricted to well‐differentiated tumours of lower gastrointestinal tract origin and is most frequent in Merkel cell carcinoma among poorly differentiated carcinomas

Abstract

Aims Special AT‐rich sequence‐binding protein 2 (SATB2) is a transcriptional regulator with critical roles in brain, craniofacial and skeletal development. It has emerged as a key marker of lower gastrointestinal (GI) tract columnar epithelial and osteoblastic differentiation. Transcription factor immunohistochemistry is useful in assigning site of origin in well‐differentiated neuroendocrine tumours (NETs), and has had a limited role in poorly differentiated neuroendocrine carcinomas (NECs). This study sought to evaluate the role of SATB2 in assigning site of origin in neuroendocrine epithelial neoplasms. Methods and results Tissue microarrays were constructed from the following: 317 NETs (37 thyroid, 46 lung, 16 stomach, 12 duodenum, 70 pancreas, 106 jejunoileum, 24 appendix, and six rectosigmoid), 44 phaeochromocytomas/paragangliomas, and 79 NECs (29 Merkel cell, 30 lung, and 20 extrapulmonary visceral); nine appendiceal and 19 rectal NETs were examined in whole sections. SATB2 immunohistochemistry was scored for extent (%) and intensity (0–3+), with an H‐score being calculated. SATB2 was expressed by 96% of rectosigmoid NETs, 79% of appendiceal NETs, and only 7% of other well‐differentiated neoplasms (P < 0.0001). Expression in lower GI tract NETs (median H‐score of 255) was stronger than in other positive tumours (median H‐score of 7) (P < 0.0001). Any SATB2 expression was 86% sensitive/93% specific for lower GI tract origin. SATB2 was expressed by 79% of Merkel cell carcinomas (median H‐score of 300), 33% of lung NECs (median H‐score of 23), and 60% of extrapulmonary visceral NECs (median H‐score of 110), with stronger expression in Merkel cell carcinoma (P < 0.001). At an H‐score cutoff of ≥150, SATB2 was 69% sensitive/90% specific for Merkel cell carcinoma. Conclusions SATB2 is frequently and strongly expressed by lower GI tract NETs; we have adopted it as our rectal NET marker. Relatively frequent and strong expression in Merkel cell carcinoma may have value in assigning NEC site of origin.

Immunohistochemistry and special stains in gastrointestinal pathology practice

“…15 SATB2 is highly sensitive and specific for lower gastrointestinal tract origin of a neuroendocrine tumour, particularly for well-differentiated neoplasms. 16 Neuroendocrine carcinoma of the lower gastrointestinal tract demonstrates similar high expression, however metastasis from a non-gastrointestinal Multiple possibilities: CK7, CK20, TTF1, CDX2, SATB2, GATA3, PAX8, ER, calretinin, CK5/6, S100, SOX10, CD3, CD20 EBV, Epsten-Barr virus; MMR, mismatch repair; IBD, inflammatory bowel disease; IPMN, intraductal papillary mucinous neoplasm.…”

“…MINI-SYMPOSIUM: GASTROINTESTINAL/HEPATO-PANCREATO-BILIARY PATHOLOGY site needs to be excluded. 16 SATB2 also allows for separation of primary small intestinal adenocarcinoma from colorectal carcinoma that has spread to the small intestine. While most primary colorectal carcinomas express this protein, less than half of primary small intestinal adenocarcinomas do.…”

SATB2 is a novel biomarker and therapeutic target for cancer

“…51 Higher expression of SATB2 gene has been reported in Merkle cell carcinoma, pancreatic, breast, colon, rectal and liver cancer patients than normal counterparts. 7-9,20,26, [52][53][54][55] The combination of SATB2 and CK20 was found to identify more than 95% of colorectal cancer. 52 Another study using 50 paired colorectal and normal tissues has reported an increased expression of SATB2 in colorectal cancer tissues.…”

“…SATB2‐associated syndrome (SAS) is an autosomal‐dominant neurodevelopmental disorder caused by changes in the gene expression of SATB2 51 . Higher expression of SATB2 gene has been reported in Merkle cell carcinoma, pancreatic, breast, colon, rectal and liver cancer patients than normal counterparts 7‐9,20,26,52‐55 . The combination of SATB2 and CK20 was found to identify more than 95% of colorectal cancer 52 .…”

Small Bowel Adenocarcinomas Featuring Special AT-Rich Sequence-Binding Protein 2 (SATB2) Expression and a Colorectal Cancer-Like Immunophenotype: A Potential Diagnostic Pitfall

“…It is also positive in 83–85% of CRCs and in 75% of appendiceal adenocarcinomas, while it is uncommonly expressed in adenocarcinomas of gastric and pancreatic origin [ 20 , 21 ]. Therefore, it has been recently proposed as a new highly tissue-specific and sensitive marker of lower intestinal tract origin in both adenocarcinomas and well-differentiated neuroendocrine tumors [ 21 , 22 ]. However, a fraction (up to 46%) of SBAs have been reported to exhibit SATB2 positivity [ 16 , 21 , 23 ], although studies on SATB2 expression in SBA are limited to relatively small series, which include very few SBAs associated with Crohn’s or celiac diseases.…”