Abstract
Currently, clinico-pathological staging and classification of residual tumor are the most important prognostic factors for clinical outcome in esophageal cancer. Nevertheless, patients with similar stages of the disease show a marked discrepancy in survival. Several new molecular prognostic factors are being evaluated in the hope that they may contribute to better assessment of the survival probability and, consequently, the tailoring of treatment. The rate of tumor growth depends on the balance between cell proliferation and death. Cell cycle regulating protein; p53 and apoptosis related protein; bax play important roles in apoptotic pathway through controlling this balance. Aims: The purpose of the present study was to examine the expression of p53 and bax in multistage esophageal tumorigensis ranging from normal mucosa to invasive esophageal squamous cell carcinoma (SCC), and to evaluate the relationship between their expressions and clinico-pathological prognostic parameters. Materials & Methods: We investigated p53 and bax expressions retrospectively in SCC. This study included 5 cases of normal esophageal mucosa, 4 cases of dysplastic epithelium, 6 cases of in situ carcinoma and 28 cases of resected esophageal carcinoma. All specimens were formalin-fixed, paraffin-embedded tissues. Immunostaining for p53 and bax proteins was done using avidin-biotin peroxidase technique. Results: There was statistically significant decrease in bax expression as the lesion progress from dysplasia through in situ to invasive esophageal tumor (P< 0.01). As regard to the differentiation there was also significant decrease in bax expression with poorer differentiation of the tumor (P< 0.01). Considering the depth of invasion; our results showed statistically significant decrease in bax expression as the stage becomes more advanced from T1 to T4 (P< 0.01). We found statistically significant increase in p53 expression as the lesion progress from dysplasia through in situ to invasive esophageal tumor (P< 0.01). There was no statistically significant difference in p53 expression between well differentiated, moderately differentiated, and poorly differentiated tumors (P < 0.4). There was also no statistically significant difference in p53 expression as the stage of the tumor becomes more advanced from T1to T4 (P< 0.9).
Conclusions: Our data suggests that: 1- decreased bax expression in esophageal pre-invasive lesions is a deleterious indicator of invasion and disease progression. 2- p53 gene mutation with subsequent over-expression occurs, relatively early in the development of esophageal SCC, but it has no role in predicting tumor outcome