Background: The purpose of this study was to investigate the significance of CD44 variant 6 (CD44v6) in predicting the treatment outcome of locally advanced adenocarcinoma of the rectum after total mesorectal excision (TME).
Methods: Expression of CD44v6 protein was detected using immunohistochemistry in 179 patients with pathologically confirmed stage II or III rectal adenocarcinoma. All patients were treated with TME, and neither neoadjuvant nor adjuvant radiotherapy were used. The correlation between the expression of CD44v6 and other disease-related characteristics with treatment outcome was investigated.
Results: The 5-year overall survival and disease-free survival rates were 66.75% and 65.77%, respectively, and the overall locoregional recurrence rate was 8.13% for the entire group of patients. CD44v6 was present in 41.9% of all patients. Multivariate analysis revealed that CD44v6 status and pelvic nodal metastasis were independent risk factors for the rate of distant metastases (P = 0.036 and 0.035, respectively), disease-free survival (P = 0.009 and 0.016, respectively), and overall survival (P = 0.048 and 0.034, respectively). Lymph node metastasis was the only independent risk factor for locoregional recurrence (P = 0.048), and a trend was found for CD44v6 on predicting the locoregional recurrence (P = 0.06) with both stage II and III diseases. CD44v6 is significantly associated with locoregional recurrence in stage III rectal cancer (hazard ratio 6.02, 95% confidence interval 1.25-29.0; P = 0.018), and the overall locoregional recurrence was significantly higher for patients with positive expression of CD44v6 than for those with negative expression (17.63% vs 6.62%; P = 0.026).
Conclusion: CD44v6 expression in cancer cells is a sensitive marker for predicting the treatment outcome in patients with stage II and III adenocarcinoma of the rectum after TME and may be used to determine the necessity of adjuvant treatment. However, further investigations are needed to determine the clinical application of CD44v6 and its reliability.