Clinical Implications of Fas/Fas Ligand Expression in Patients with Esophageal Squamous Cell Carcinoma Following Neoadjuvant Chemoradiotherapy

Recent epidemiological studies demonstrated that the incidence of esophageal squamous cell carcinoma (ESCC) is on the increase. Although neoadjuvant chemoradiotherapy (CRT) followed by surgery may improve long-term survival and reduce local recurrence in patients with esophageal cancer, the overall cure rate of esophageal cancer is low. Fas/Fas ligand (FasL) signaling initiates the cell death pathway. The roles of FasL in tumor growth, progression and resistance to treatment have been demonstrated in several malignancies. The aim of this preliminary study was to evaluate Fas/FasL expression in ESCC with neoadjuvant CRT. A total of 20 patients who received neoadjuvant CRT (30-40 Gy; 5-fluorouracil plus cisplatin followed by surgery) were enrolled. We evaluated the expression of Fas, FasL and Ki67 (a proliferative marker) using immunohistochemistry and analyzed the correlations between their expression and clinical outcomes. Additionally, we investigated the association of Fas/FasL expression with peritumoral immune CD8-positive and Foxp3-positive cells. High FasL expression was significantly correlated with disease recurrence (P=0.0134). Patients with high FasL expression exhibited poorer recurrence-free and overall survival (P=0.0102 and 0.0385, respectively). Patients with low Fas and high FasL exhibited significantly poorer recurrence-free survival (P=0.0035). Although statistical significance was not reached, Fas expression appeared to be inversely correlated with Foxp3-positive cells and FasL expression appeared to be inversely correlated with CD8-positive cells. In conclusion, FasL expression was associated with tumor relapse and poor prognosis in patients with ESCC following CRT. Pharmacological control of Fas/FasL signaling may improve therapeutic efficacy and outcome in ESCC patients receiving preoperative CRT.