Prognostic significance of CDX2 immunoexpression in poorly differentiated clusters of colorectal carcinoma

CDX2 is a transcription factor that acts as a tumor suppressor in colorectal cancer (CRC). Its loss triggers metastatic process and tumor progression; however, its prognostic role in patients with CRC is still controversial. Poorly differentiated clusters (PDCs) are aggregates of neoplastic cells which likely have high metastatic potential in CRC. In this study, we analyzed and compared CDX2 expression in PDC (CDX2-PDC) and corresponding main tumor (CDX2 main tumor) in 42 CRCs showing at least 10 PDC (PDC G3). Five of 42 CRCs (12%) were classified as CDX2 main tumor negative (4/5 were also PDC-CDX2 negative); all had tumor recurrence and died of CRC. Twenty nine of 42 cases were CDX2-PDC negative. Among CRC CDX2 main tumor positive, 15 had recurrences and 13 died from CRC; 13 and 11 of them, respectively, were CDX2-PDC negative. By assigning one point to CDX2 main tumor or CDX2-PDC positivity, we assessed CDX2-staining score for each case. Twelve cases had CDX2-staining score 2 (CDX2 positive in main tumor and PDC); 26 had score 1 (CDX2 positive in main tumor or PDC), and 4 had CDX2 score 0 (CDX2 negative in main tumor and PDC). In our patients, CDX2-staining score had higher prognostic value compared to CDX2 main tumor or CDX2-PDC alone. In addition, it represented a significant and independent prognostic variable for disease-free survival (DFS) and cancer-specific survival (CSS). Our findings suggest that, although loss of CDX2 in the main tumor identifies high-risk patients with high specificity, CDX2-PDC should also be considered in CDX2 main tumor positive cases to predict prognosis.