Association of Caudal-Type Homeobox 2 Immunohistochemical Expression With Pathological Stage, Tumor Grade, and Histological Subtype in Colorectal Malignancies: A Single-Center Observational Study

BackgroundCaudal-type homeobox 2 (CDX2) is a nuclear transcription factor that maintains intestinal epithelial differentiation.Reduced CDX2 expression has been associated with adverse pathological features and inferior outcomes in colorectal cancer, but its clinicopathological value depends on the scoring method and tumor context. MethodsThis single-center observational study evaluated 50 histopathologically confirmed colorectal malignancies.CDX2 immunohistochemistry was scored semi-quantitatively by multiplying nuclear staining proportion (0-4) by staining intensity (0-3), yielding an immunoreactivity score (IRS) of 0-12.Low/reduced expression was defined as IRS ≤4 and high/preserved expression as IRS ≥5.The patient-level master chart was used to summarize IRS and its associations with stage and grade; the histology comparison retained the original aggregated subtype counts.Exact tests used evaluable cases; pooled stage/grade analyses were exploratory, and subtype analysis was limited to major adenocarcinomas.The primary analytical endpoint was the association between CDX2 expression and pathological stage.The original pathology records for six cases recorded as pTis with N1/N2 disease were rechecked, and a conservative sensitivity analysis excluding these records was performed. ResultsCDX2 was evaluable in 48 of 50 cases; 29/48 (60.4%) showed low expression and 19/48 (39.6%) showed high expression.Median IRS was 2 (range 0-12).Among 43 cases with complete stage information and evaluable CDX2, low expression increased from 44.4% in stage 0, 30.0% in stage I, and 40.0% in stage II to 83.3% in stage III and 100% in the single stage IV case (Fisher-Freeman-Halton p=0.023).Advanced stage was associated with higher odds of low CDX2 expression (odds ratio (OR) 8.89, 95% confidence interval (CI) 2.01-39.22;p=0.004), although the wide confidence interval indicates imprecision.All 19 high-grade tumors showed low CDX2, compared with 9/27 (33.3%) low-grade tumors and 1/2 (50.0%) intermediate-grade tumors (p<0.001).Low CDX2 was also more frequent in mucinous adenocarcinoma (8/10, 80.0%) and signetring cell carcinoma (5/5, 100%) than in conventional adenocarcinoma (10/22, 45.5%; p=0.026).Pathology records confirmed that six entries combined primary lesions documented as pTis with separately submitted regional lymph nodes containing metastatic tumor.In a conservative sensitivity analysis excluding these six records, the early-versus-advanced-stage association persisted (low CDX2: 10/13 (76.9%) versus 9/24 (37.5%);OR 5.56, 95% CI 1.20-25.71;two-sided Fisher's exact p=0.038), whereas the overall five-stage association is not statistically significant (exact p=0.182). ConclusionReduced CDX2 expression tracked closely with advanced pathological stage, high tumor grade, and aggressive adenocarcinoma morphology.These findings support CDX2 as a practical adjunct marker of adverse tumor biology in colorectal malignancies.Because survival, recurrence, and molecular profiling were not evaluated, the present study supports clinicopathological prognostic association rather than independent survival prognostication.Because the cohort included different tumor classes and the detailed five-stage result was sensitive to the handling of six nonstandard pTis/node-positive records, the stage and grade findings should be considered exploratory.