Expression of apoptosis-related proteins and response to chemoradiotherapy and prognosis in esophageal cancer

Purpose

Defects in the apoptotic pathway confer insensitiviry to the cytotoxic effects of chemotherapy and hence represent an important distal mechanism for the development of chemoresistance. In this study, we sought to obtain results on which to base clinical hypotheses about this mechanism. The aim of this study was to analyze the correlation of the expression of three of these apoptotic molecules, Bc1-2, Bax and Bc1-X, with chemoradiotherapy response and clinical outcome in patients with esophageal tumors.

Patients and methods

Tumor biopsy specimens from 42 patients were assessed by immunohistochemistry for expression of Bc1-2, Bax and Bc1-X proteins. The expression of these proteins was correlated with response to chemoradiotherapy in 24 patients.

Results

The overall expression of Bc1-2, Bax and Bc1-X was 29%, 68% and 88%, respectively. Bax expression was lower in lymph-node-positive tumors (p = 0.01). Probability of response to chemoradiotherapy was higher in Bax-negative tumors than in Bax-positive tumors (80% vs 35%, p = 0.1). In addition, 62% of patients with low Bc1-X expression (< 50% stained cells) showed response to chemoradiotherapy, as opposed to only 33% of patients with higher Bc1-X expression (p = 0.2). Patients with low Bc1-X expression showed a significantly better prognosis than those with high Bc1-X expression (p =0.02), and a tendency towards higher survival was detected in Bc1-2 positive patients.

Conclusion

The correlation detected between Bax and Bc1-X expression and response to chemoradiotherapy suggests that screening for these apoptosisrelated proteins could be useful in determining patients who would benefit from chemoradiotherapy. However, further investigation is warranted to elucidate the potential role of Bax in taxane-treated patients. Clearly, since high Bc1-X expression conferred poor survival in our study, it could be a useful prognostic marker in esophageal cancer.