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Low Expression of Bax Predicts Poor Prognosis in Patients with Locally Advanced Esophageal Cancer Treated with Definitive Chemoradiotherapy

Authors' Affiliations: Departments of ¹ Hematology-Oncology, ² Pathology, ³ Gastroenterology, ⁴ Radiation Oncology, and ⁵ Section of Clinical Epidemiology and Biostatistics in Clinical Trial Center, Ajou University School of Medicine, Suwon, Republic of Korea; and ⁶ Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea

Requests for reprints: Jin-Hyuk Choi, Department of Hematology-Oncology, Ajou University School of Medicine, Suwon, 443-721, Republic of Korea. Phone: 82-31-219-4920; Fax: 82-31-219-5983; E-mail: jhchoimd{at}ajou.ac.kr.

Purpose: The present study evaluated the prognostic significance of apoptosis-related proteins, p53, Bcl-2, Bax, and galectin-3 in patients with locally advanced esophageal cancer treated with definitive chemoradiotherapy.

Experimental Design: A total of 63 patients with locally advanced esophageal cancer (squamous cell carcinoma: 62; adenocarcinoma: 1; stages II-IV) were treated with definitive chemoradiotherapy using 5-fluorouracil and cisplatin combined with radiotherapy. Pretreatment tumor biopsy specimens were analyzed for p53, Bcl-2, Bax, and galectin-3 expression by immunohistochemistry.

Results: High expression of Bax, p53, Bcl-2, and galectin-3 was observed in 67%, 47%, 24%, and 29% of patients, respectively. The median overall survival (OS) of total patients was 14 months with 16% of 3-year OS. High expression of p53, Bcl-2, and galectin-3 did not show correlation with clinicopathologic characteristics, including patient outcome. Low expression of Bax was significantly correlated with lack of clinical complete response (P = 0.023). Low expression of Bax was also associated with poor OS (median, 8 months versus 16 months; P = 0.0008) in univariate analysis. In multivariate analysis, low expression of Bax was the most significant independent predictor of poor OS (P = 0.009), followed by low dose intensity of cisplatin and lack of clinical complete response.

Conclusions: Low expression of Bax was significantly associated with the poor survival of patients with locally advanced esophageal cancer treated with chemoradiotherapy using 5-fluorouracil and cisplatin. Immunohistochemical staining for Bax with a pretreatment biopsy specimen might be useful to select the optimal treatment options for these patients.

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