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Molecular biology of esophageal adenocarcinoma (EAC) is not fully elucidated. The aim of this study was to assess the expression of cycle regulator and tumor suppressor p16 in esophageal adenocarcinoma. The expression of p16 at protein and gene level was investigated using immunohistochemistry and fluorescence in situ hybridization in thirteen EAC specimens obtained by endoscopic biopsies and surgical resections. The mean age of enrolled patients was 62 years and a male predominance was observed. Loss of p16 protein expression was detected in 77% of the cases and loss of p16 gene was found in 69% of cases as hemizygous deletion was the most common. Significant correlation was found between the absence of p16 protein expression and p16 allelic loss. Cell cycle disturbances seem to play role in the EAC carcinogenesis and probably p16 gene deletions are connected with the loss of p16 protein expression.


Background: The proteins p16, p53, Bcl-2, and Bax are important cell cycle and apoptotic regulators involved in carcinogenesis and found to have prognostic significance in various cancers. However, the data for squamous cell carcinoma of oral cavity (OSCC) and of oropharynx (OPSCC) are conflicting.

Objective: We sought to determine if expression of p16, p53, Bcl-2, and Bax expression are associated with 5-year overall survival (OS) of patients with OSCC and OPSCC.

Methods: One-hundred thirty-seven cases of OSCC and 140 cases of OPSCC diagnosed from January 2002 to December 2004 at Songklanagrind Hospital, Songkhla, Thailand, were analyzed using a Cox proportional hazards model for 5-year OS in relation to immunohistochemical detection of Bcl-2, Bax, p53, and p16 proteins.

Results: The frequencies of p16, p53, Bcl-2, and Bax expression in OSCC were 13%, 45%, 4%, and 66%, and in OPSCC were 18%, 53%, 22%, and 75%, respectively. In univariate analysis, clinical variables including T stage, N stage and treatment were significantly associated with survival. In multivariate Cox regression, Bax overexpression was significantly associated with poor survival both in OSCC (HR 1.77, 95% CI 1.04-3.01) and in OPSCC (HR 2.21, 95% CI 1.00-4.85). We found no significant association of p16, Bcl-2, and p53 expression with survival.

Conclusion: The expression pattern of p16, p53, Bcl-2, and Bax are similar in OSCC and OPSCC. Only Bax expression has prognostic significance for both tumor sites.