Wen Wang1, Luyan Shen1, Yu Sun2, Bin Dong2, Keneng Chen1. 1. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Surgery I, Peking University Cancer Hospital & Institute Beijing, China. 2. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Pathology, Peking University Cancer Hospital & Institute Beijing, China.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
BACKGROUND: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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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 cancerpatients.
Authors: Junxia Min; Alexander Zaslavsky; Giuseppe Fedele; Sara K McLaughlin; Elizabeth E Reczek; Thomas De Raedt; Isil Guney; David E Strochlic; Laura E Macconaill; Rameen Beroukhim; Roderick T Bronson; Sandra Ryeom; William C Hahn; Massimo Loda; Karen Cichowski Journal: Nat Med Date: 2010-02-14 Impact factor: 53.440
Authors: Val Gebski; Bryan Burmeister; B Mark Smithers; Kerwyn Foo; John Zalcberg; John Simes Journal: Lancet Oncol Date: 2007-03 Impact factor: 41.316