Pattern of expression of CDX2 in colorectal cancer and its role in prognosis

CDX2, a nuclear protein, is essential for the proliferation and development of intestinal epithelial cells and is frequently down-regulated during tumorigenesis. We have evaluated the pattern of CDX2 expression in all stages of colorectal cancer (CRC) and its association with prognosis.

We performed CDX2 staining by immunohistochemistry (IHC) on the available biopsy blocks of patients of CRC registered in our institute from January 2014 to January 2018. CDX2 scoring was done using the semi-quantitative method.

A total of 286 patients were registered during the study period, of which only 110 biopsy blocks were available for staining. Of 110 patients, 77 (70%) had colon cancer and 33 (30%) had rectal cancer. The median age was 54.2 years, with 62 (56.4%) being male and 48 (43.6%) female with a male to female ratio of 1.3:1. In the study cohort, 33 (30%) patients had stage II disease, 30 (27.3%) had stage III, and 47 (42.7%) had stage IV. Seventy-three (66.4%) were positive for CDX2 and 37 (33.4%) were negative. Loss of CDX2 expression was significantly associated with advanced stage, rectal site, poor grade of differentiation, and presence of lymphovascular invasion. With a median follow-up of 16 months, progression-free survival (PFS) at 2 years was 30% for CDX2-negative patients compared to 67% for CDX2-positive patients (P = 0.009), whereas the overall survival (OS) at 2 years was 46% for CDX2-negative versus 77% for CDX2-positive patients (P = 0.01).

Loss of CDX2 expression is associated with advanced stage, higher tumor grade, presence of LVSI, worse PFS, and OS and thereby functions as a poor prognostic factor in CRC.