Use of SATB2 and CDX2 Immunohistochemistry to Characterize and Diagnose Colorectal Cancer

Abstract

SATB2 has been reported to be highly specific for lower gastrointestinal tract tumors. On the basis of its ileum–colon conversion effects, which involve the activation of colonic genes in cooperation with CDX2 and HNF4A, we hypothesized that SATB2 and CDX2 might define the characteristics of colorectal cancers (CRCs). In the present study, the clinicopathologic and immunohistochemical characteristics of 269 CRCs were analyzed according to SATB2 and CDX2 expression. CRCs with SATB2− and/or CDX2− phenotypes showed associations with poorly differentiated histotypes (P<0.00001), mucus production (P=0.0019), and mismatch repair-deficient phenotypes (P<0.00001). SATB2−/CDX2− CRCs were significantly associated with CK20-negativity, with or without CK7 expression (P<0.00001), as well as with MUC5AC-positivity (P<0.00001), and CD10-negativity (P=0.00047). Negativity for SATB2 or CDX2 was associated with the expression of PD-L1 in both all CRC (P<0.00001) and mismatch repair-proficient CRC (P=0.000091). Multivariate Cox hazard regression analysis identified negativity for SATB2 and/or CDX2 as potential independent risk factors for patients with CRC. Regarding the diagnostic utility of SATB2, all of the 44 CRC metastases could be diagnosed as colorectal in origin if the immunohistochemical phenotypes (including CK7, CK20, and p53) of the primary lesions and patient history were considered. Among the other 684 tumors, we were unable to distinguish a case of CK7−/CK20+/CDX2+/SATB2+ ovarian mucinous cystadenocarcinoma from metastatic CRC without the patient history and clinical information.