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

• Published in: Clinical cancer research 1998-12, Vol.4 (12), p.2991-2997
• Main Authors: SARBIA, M, STAHL, M, FINK, U, WILLERS, R, SEEBER, S, GABBERT, H. E
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antineoplastic agents; bcl-2-Associated X Protein; bcl-X Protein; Biological and medical sciences; Biomarkers, Tumor - biosynthesis; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; Carcinoma, Squamous Cell - therapy; Combined Modality Therapy; Combined treatments (chemotherapy of immunotherapy associated with an other treatment); Epithelium - metabolism; Esophageal Neoplasms - metabolism; Esophageal Neoplasms - pathology; Esophageal Neoplasms - therapy; Esophagus - metabolism; Female; Humans; Immunohistochemistry; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Prognosis; Proto-Oncogene Proteins - biosynthesis; Proto-Oncogene Proteins c-bcl-2 - biosynthesis; Retrospective Studies; Survival Rate; Tumor Suppressor Protein p53 - biosynthesis
• ISSN: 1078-0432; 1557-3265

The present study retrospectively examines the correlation between the outcome of patients with locally advanced esophageal squamous cell carcinoma (LAEC) after multimodal treatment (radiochemotherapy +/- surgery) and the expression 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. Pretreatment tumor biopsies were immunohistochemically investigated for expression of p53, Bcl-2, Bax (bcl-2-associated X protein), and Bcl-X(L) (bcl-2-related X protein). The overall expression of p53, Bcl-2, Bax, 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 and 52.6%, respectively) than tumors positive for p53 expression and tumors with strong Bcl-X(L) expression (30.0 and 31.6%, respectively); however, these differences did not attain statistical significance. No correlations were found between the expression of Bcl-2 and Bax and the response to chemotherapy. In patients treated by radiochemotherapy and surgery, p53-negative tumors 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 significant), whereas no differences in survival were observed in relation to the expression of Bax or Bcl-X(L). No differences in survival were observed in patients treated by radiochemotherapy without subsequent resection therapy in relation to the expression of apoptosis-regulating proteins. Immunohistochemical examination of pretherapeutic tumor biopsies for expression of apoptosis-regulating proteins may help to identify patients with LAEC who may benefit from multimodal treatment and those who may not.