Colorectal cancer (CRC) is the third most common malignancy and the second leading cause of cancer death in the world [1]. The tumor, node, metastasis (TNM) staging is globally used for the prediction of survival in patients with CRC, but a considerable variation in survival exists in patients of the same cancer stage [2,3]. For patients of the same stage, prognostic factors play an important role in identifying patients with high risk of cancer recurrence or death from cancer. Besides known prognostic factors, including tumor differentiation, lymphovascular emboli, perineural invasion, tumor-infiltrating lymphocyte (TIL) [4], tumor to stroma ratio [5,6], and microsatellite instability (MSI), caudal-type homeobox transcription factor 2 (CDX2) has gained an attention as a prognostic marker in patients with CRC. Loss of CDX2 expression has been shown to be associated with worse clinical outcome in patients with CRC [[7], [8], [9]].

Expression of CDX2 is confined to the small intestine and the large intestine and found in 90 % of CRCs [7,10]. In retrospective studies, CDX2 loss has been demonstrated to be not only a prognostic marker [9] but also a predictor of positive response to chemotherapy in patients with stage II colon cancer [11] or negative response in patients with metastatic CRC [12]. Similarly, the special AT-rich sequence binding protein 2 (SATB2) has been demonstrated to be a useful biomarker for identifying a colorectal origin in metastatic adenocarcinoma [10,13,14] and decreased or loss-of expression of SATB2 has been associated with poor prognosis in patients with CRC [[15], [16], [17]]. Because of a strong correlation in CRCs between CDX2- and SATB2-expression [18,19], CRCs with decreased or loss-of expression of SATB2 are expected to share clinicopathological features with CRCs with decreased or loss-of expression of CDX2, including proximal location of tumor, poor differentiation, and an association with microsatellite instability (MSI) or CpG island methylator phenotype (CIMP) [7,18]. Although SATB2 loss has been associated with poor prognosis in patients with CRC, it is unclear whether the poor prognosis is attributed to concomitant CDX2 loss and whether concomitant loss of SATB2 loss may harbor a prognostic implication in CRCs with CDX2 loss.

In the present study, we analyzed archival tissue samples of CRC for their expression status in CDX2 and SATB2 using immunohistochemistry and correlated their expression statuses with clinicopathological features. The analyzed tumor samples were obtained from patients with stage III CRC who received adjuvant fluoropyrimidine plus oxaliplatin. We hypothesized that the prognostic implication of CDX2 loss might be affected by concomitant SATB2 loss. To investigate the effects of the interaction between CDX2 loss and SATB2 loss on survival, the combination of CDX2 loss and SATB2 loss was examined for their relationship with survival and clinicopathological features. On survival analysis, not CRCs with isolated loss of CDX2 or SATB2, but CRCs with concomitant loss of CDX2 and SATB2 were associated with poor prognosis.