Predictive effect of p53 and p21 alteration on chemotherapy response and survival in locally advanced adenocarcinoma of the esophagus

Abstract

Background: Cell cycle regulating proteins (p53/p21) and proliferation index Ki-67 have been associated with prognosis and response to chemotherapy. The aim of this study was to determine the significance of these molecular markers on tumor response and prognostic effect in a group of esophageal cancer patients treated with neoadjuvant chemotherapy.

Patients and methods: Immunohistochemical expression of p53/p21 and Ki-67 was examined in pre-treatment biopsy specimen of 30 patients, in phase II neoadjuvant studies for locally advanced adenocarcinoma of the esophagus, who underwent surgery. Seven patients (23%) had progressive disease. Resection was achieved in all responders (n=23; 77%) and histochemical expression of the above-mentioned proliferating markers was examined in pre-treatment and resection specimens after chemotherapy.

Results: Responders had a significantly better survival compared to non-responders (p=0.001). Expression of p53, p21 and high Ki-67 in pre-treatment specimens was 73% (22/30), 63% (19/30) and 30% (10/30), respectively and was not related to response to chemotherapy. However, alteration in expression of p53-positivity in the pre-treatment specimens to p53-negativity in the resection specimens and p21-negativity to p21-positivity in 6 of the 23 (26%) resected tumors was correlated with better response and survival (p=0.011).

Conclusion: Data from this study showed that alteration of p53 and p21 expression rather than the initial expression seems to be related to chemotherapy response and overall survival in patients with esophageal adenocarcinoma.