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J Thorac Cardiovasc Surg 2008;135:1029-1035
© 2008 The American Association for Thoracic Surgery

General Thoracic Surgery

Reduced membranous β-catenin protein expression is associated with metastasis and poor prognosis in squamous cell carcinoma of the esophagus

Po-Kuei Hsu, MDa, Anna Fen-Yau Li, MD, PhDb, Yi-Ching Wang, PhDc, Chih-Cheng Hsieh, MDa, Min-Hsiung Huang, MDa, Wen-Hu Hsu, MDa, Han-Shui Hsu, MD, PhDa,*

a Division of Thoracic Surgery, Department of Surgery, Taipei Veterans General Hospital, National Yang-Ming University, School of Medicine, Taipei, Taiwan
b Department of Pathology, Taipei Veterans General Hospital, National Yang-Ming University, School of Medicine, Taipei, Taiwan
c Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan

Received for publication July 10, 2007; revisions received August 29, 2007; accepted for publication November 9, 2007.

* Address for reprints: Han-Shui Hsu, MD, PhD, Division of Thoracic Surgery, Department of Surgery, Taipei Veterans General Hospital, No. 201, Sec. 2, Shih-Pai Road, Taipei, Taiwan. (Email: hsuhs{at}vghtpe.gov.tw).

Objectives: The aim of this study was to evaluate, by immunohistochemical analysis, the protein expression of β-catenin and p53 in resected esophageal squamous cell carcinoma specimens. The clinical relevance and prognostic significance of the expression of these proteins were also analyzed.

Methods: Immunohistochemistry was performed on paraffin-embedded tissue specimens from 68 resected esophageal squamous cell carcinoma tumor specimens to detect the expression of β-catenin and p53. The correlation between the results of immunoexpression and the clinicopathologic parameters and patient survival was processed statistically.

Results: Reduced membranous β-catenin expression was noted in 43 (63.2%) of 68 tumor specimens. Increased expression of p53 was observed in 43 (63.2%) of 68 specimens. Reduced membranous β-catenin protein expression was associated with the presence of distant metastasis (P = .006). Patients with reduced membranous β-catenin expression had a worse prognosis than patients with normal membranous β-catenin expression (P = .005). Patients with combined increased p53 and reduced membranous β-catenin protein expression had the worst prognosis (P = .012). In a multivariate survival analysis, reduced membranous β-catenin expression and nodal involvement were independent prognostic factors (P = .004 and .019, respectively).

Conclusions: Immunohistochemical analysis revealed that reduced membranous β-catenin protein expression was associated with the presence of distant metastasis and a poor prognosis in patients with esophageal squamous cell carcinoma. Combined increased p53 and reduced membranous β-catenin protein expression indicated a very poor prognosis in patients with esophageal squamous cell carcinoma. Further investigation is needed to understand the roles of β-catenin and p53 in the tumorigenesis and metastasis of esophageal squamous cell carcinoma.

Abbreviations and Acronyms ESCC = esophageal squamous cell carcinoma; GSK3β = glycogen synthase kinase 3β






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