ABSTRACT
BACKGROUND: The aim of the present study was to validate the prognostic impact of CDX2 in patients with stage II colon cancer. METHODS: Two unbiased population-based cohorts representing all patients operated for stage II colon cancer in Denmark in 2002 and 2003. The CDX2 expression was evaluated by immunohistochemistry on whole tumour sections. Patients were classified into three groups, CDX2-positive, -moderate, and -negative, for comparison with the clinical data. RESULTS: A total of 1157 patients were included. We found a significant relationship between loss of CDX2 expression and poor disease-free survival in both cohorts, p = 0.0267 and 0.0118, respectively. Five-year disease-free survival rates were 66%, 72% and 74% in the first cohort and 62%, 65%, and 75% in the second cohort for the negative, moderate, and positive CDX2 expression groups, respectively. Multiple Cox regression analysis performed on the combined cohorts confirmed an independent prognostic impact of CDX2 on disease-free survival, hazard ratio 1.543 (95% confidence interval 1.129-2.108), p = 0.0065. CONCLUSIONS: This retrospective study provides validation regarding the prognostic impact of CDX2 in patients with stage II colon cancer. The results justify prospective validation clarifying its clinical impact.
Subject(s)
CDX2 Transcription Factor/metabolism , Colonic Neoplasms/metabolism , Aged , CDX2 Transcription Factor/genetics , Cohort Studies , Colonic Neoplasms/epidemiology , Colonic Neoplasms/pathology , Denmark/epidemiology , Female , Humans , Male , Middle Aged , Prognosis , Recurrence , Registries , Reproducibility of ResultsABSTRACT
PURPOSE: High-risk patients with stage II colon cancer (CC) may benefit from adjuvant chemotherapy, but additional prognostic markers are needed for better stratification. We investigated the prognostic value of tumour stroma ratio (TSR) and tumour budding (TB). METHODS: A nationwide population-based cohort of 573 patients with stage II CC was included. TSR was scored on hematoxylin and eosin sections as low TSR (> 50% stroma) and high TSR (≤ 50% stroma). TB was evaluated in hotspots on pan-cytokeratin stained sections in 10 high power fields (HPF) at the invasive front and classified by the mean number of buds per HPF as high grade budding (≥ 10 buds) or low-grade budding (< 10 buds). The prognostic value was investigated in Cox proportional hazard models for recurrence-free survival (RFS) and overall survival (OS). RESULTS: Low TSR was associated with worse RFS (HR = 1.342 (95% CI 1.006-1.791), p = 0.045) and OS (HR = 1.376 (95% CI 1.016-1.862), p = 0.039). Furthermore, an association was found between low TSR and microsatellite stabile tumours (p < 0.001). The mean number of buds per HPF was associated to TSR with increasing number of buds related to a lower TSR (p = 0.026). No statistically significant prognostic impact of TB regarding OS or RFS was detected. CONCLUSIONS: TSR provided valuable prognostic information, and adding TSR to the current risk stratification may contribute to better patient selection. The estimates of TSR and TB were found to be associated, but no prognostic value of TB was documented.
