SATB2 Is Superior to CDX2 in Distinguishing Signet Ring Cell Carcinoma of the Upper Gastrointestinal Tract and Lower Gastrointestinal Tract

Abstract

Signet ring cell carcinomas of the gastrointestinal (GI) tract are clinically aggressive neoplasms with frequent intra-abdominal metastases at initial presentation. Currently available immunohistochemistry (IHC) markers cannot distinguish signet ring cell carcinomas of the lower GI tract and upper GI tract, suggesting the need for more specific diagnostic markers. SATB2 is a novel, sensitive marker for colorectal carcinoma. We hypothesized that SATB2 IHC can reliably identify primary and metastatic signet ring cell carcinomas of lower GI tract origin. SATB2 and CDX2 IHC was performed on 159 primary (n=93) and metastatic (n=66) signet ring cell carcinomas of GI tract origin and 13 metastatic breast carcinomas with signet ring cell features. Positive SATB2 expression (SATB2+) was identified in 82% (27/33) of appendiceal, 88% (43/49) of colorectal, 13% (7/54) of gastric, and 35% (8/23) of esophageal/esophagogastric junction signet ring cell carcinomas. Primary and metastatic signet ring cell carcinomas of lower GI tract origin were more frequently SATB2+ than those from upper GI tract (70/82, 85% vs. 15/77, 19%, P<0.01). Compared with CDX2, SATB2+ and dual-positive staining for SATB2 and CDX2 both had higher specificities for signet ring cell carcinomas from the lower GI tract (81% vs. 49% and 86% vs. 49%, respectively, P<0.01 for both). Two (15%) metastatic breast carcinoma were SATB2+, but all 13 demonstrated negative CDX2 staining. In summary, our results show SATB2 is a relatively specific immunohistochemistry marker for both metastatic and primary signet ring cell carcinomas of lower GI tract origin.

A combination of the immunohistochemical markers CK7 and SATB2 is highly sensitive and specific for distinguishing primary ovarian mucinous tumors from colorectal and appendiceal metastases

“…(6,9) SATB2 has also been shown to have superior value in distinguishing certain lower from upper GI metastasis. (22,23) Of note, upper GI metastasis can have the same immunohistochemical profile as ovarian mucinous carcinomas including some pancreatic adenocarcinoma showing PAX8 expression. 24Herein, we found a higher sensitivity of SATB2 alone for colorectal adenocarcinomas expression.…”

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

“…As mentioned in the introduction, SATB2 was introduced to the diagnostic pathology community as a potential colon cancer diagnostic marker . Subsequent work has established its role as a lower GI tract‐specific columnar marker, which is especially useful in the distinction of colon cancer from variably CDX2‐expressing oesophageal, gastric, small‐intestinal and pancreatic adenocarcinomas, and in the distinction of disseminated low‐grade appendiceal mucinous neoplasm from primary mucinous ovarian tumour . Although data are limited to one study, it has also been shown to be more sensitive than CK20 and CDX2 in medullary (undifferentiated) colon cancer, with Lin et al .…”

“…16 Subsequent work has established its role as a lower GI tract-specific columnar marker, which is especially useful in the distinction of colon cancer from variably CDX2-expressing oesophageal, gastric, small-intestinal and pancreatic adenocarcinomas, and in the distinction of disseminated low-grade appendiceal mucinous neoplasm from primary mucinous ovarian tumour. 18,[23][24][25][30][31][32][33] Although data are limited to one study, it has also been shown to be more sensitive than CK20 and CDX2 in medullary (undifferentiated) colon cancer, with Lin et al reporting any staining and >50% cell staining in 89% and 75% of 18 cases, respectively. 23 This study highlights two additional diagnostic applications of SATB2 immunohistochemistrynamely, assigning a lower GI tract origin for a NET and a cutaneous origin for a NEC.…”

Immunohistochemistry and special stains in gastrointestinal pathology practice

“…Although its expression largely parallels CDX2, SATB2 is more site-specific and is less prone to methylation-related silencing than CDX2, making it more useful in mucinous, signet ring and undifferentiated colorectal carcinomas. 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.…”