Expression of apoptosis-regulating proteins and outcome of esophageal cancer patients treated by combined therapy modalities

The present study retrospectively examines the correlation between the outc ome of patients with locally advanced esophageal squamous cell carcinoma (L AEC) after multimodal treatment (radiochemotherapy +/- surgery) and the exp ression of apoptosis-regulating proteins in pretherapeutic biopsies. Thirty-eight patients with LAEC who took part in a prospective multicentric trial received radiochemotherapy, optionally followed by surgery. Pretreat ment tumor biopsies were immunohistochemically investigated for expression of p53, Bcl-2, Bar (bcl-2-associated X protein), and Bcl-X-L (bcl-2-related X protein), The overall expression of p53, Bcl-2, Bar, and Bcl-X-L was 52.6, 57.9, 100, and 97.4% respectively, Tumors without p53 expression and tumors with weak Bcl-X-L expression showed response to chemotherapy more frequently (55.6 a nd 52.6%, respectively) than tumors positive for p53 expression and tumors with strong Bcl-X-L expression (30.0 and 31.6%, respectively); however, the se differences did not attain statistical significance. No correlations wer e found between the expression of Bcl-2 and Bar and the response to chemoth erapy. In patients treated by radiochemotherapy and surgery, p53-negative t umors showed a significantly better outcome than p53-positive tumors (mean survival, 31.1 months versus 11.3 months; P = 0.0378), Additionally, a more favorable outcome was observed in tumors positive for Bcl-2 (not significa nt), whereas no differences in survival were observed in relation to the ex pression of Bar or Bcl-X-L. No differences in survival were observed in pat ients treated by radiochemotherapy without subsequent resection therapy in relation to the expression of apoptosis-regulating proteins. Immunohistochemical examination of pretherapeutic tumor biopsies for expres sion of apoptosis-regulating proteins may help to identify patients with LA EC who may benefit from multimodal treatment and those who may not.