Role of E2F-1 and its involving pathway in esophageal squamous cell carcinoma

Esophageal cancer is a lethal disease and the optimal therapy remains unclear. Neoadjuvant chemotherapy provides an increased chance of survival; therefore, we attempted to identify potential molecular markers that might improve evaluations of individual responses to therapy.

We recruited 109 patients with resectable esophageal squamous cell carcinoma. The patients underwent radical esophagectomy and did not receive any other perioperative treatment. Expression of E2F-1 and molecules involved in its targeted pathways, pERK, Bim, pRb, epidermal growth factor receptor, EZH2 and pAKT, was investigated immunohistochemically.

Correlations were observed between E2F-1 and pRb expression; EZH2 expression was significantly correlated with the degree of carcinoma differentiation (P = 0.01). Stage III patients were found to have longer survival if they did not express pERK than if they did (23 months vs. 11 months, P = 0.01). Patients with E2F-1 not expressing pRb were found to have longer survival times than those with E2F-1 who expressed pRb (18.8 months vs. 8.6 months, P = 0.021). Similarly, stage III patients with E2F-1 but not expressing pERK also survived longer than those expressing pERK (23.5 months vs. 3.9 months, P < 0.001).

A high expression of pERK was significantly associated with poor survival in patients with locally advanced esophageal cancer. Expression of a combination of molecules, rather than of individual molecules, was more predictive of disease prognosis. E2F-1 and molecules of its targeted pathways may be candidate proteins as markers of chemosensitivity in esophageal cancer patients.