ERCC1 expression and tumor regression predict survival in esophageal squamous cell carcinoma patients receiving combined trimodality therapy

Purpose

Combined trimodality therapy with neoadjuvant chemoradiation followed by surgery has shown promising results for locally advanced operable esophageal cancer. DNA repair proteins may affect treatment efficacy through repairing DNA damage induced by chemotherapy and radiation therapy. We evaluated the associations of XRCC1, ERCC1 and MGMT expression with histopathologic response and survival in patients with locally advanced operable esophageal squamous cell carcinoma (ESCC) who received neoadjuvant chemoradiation.

Methods

Paraffin-embedded pre-treatment tissue samples, collected by endoscopic biopsy from patients treated with cisplatin-based neoadjuvant chemoradiation followed by surgery, were immunohistochemically stained for XRCC1, ERCC1 and MGMT expression.

Results

Of the 44 patients, major histopathologic response was noted in 26 (59.1%) patients. 68.8% of patients with ERCC1-negative tumors had major histopathologic response, compared to 53.6% of those who expressed positive ERCC1, though the difference was not statistically significant (P = 0.361). The patients with ERCC1-negative tumor presented much better overall survival than those positive for ERCC1 expression (P = 0.018). Patients with major histopathologic response had a 3-year survival rate of 96.2% versus those with minor response, with a 3-year survival rate of 41.5% (P = 0.000). Multivariate analysis showed that ERCC1 expression and histopathologic response were independent predictive factors of overall survival in patients with locally advanced operable ESCC receiving neoadjuvant chemoradiation.

Conclusion

Patients with ERCC1-negative tumors show a benefit from neoadjuvant chemoradiation, ERCC1 expression and tumor regression are useful predictive markers in patients with locally advanced operable ESCC receiving neoadjuvant chemoradiation followed by surgery.