Coexpression of Bcl-2, c-Myc, and p53 oncoproteins as prognostic discriminants in patients with colorectal carcinoma

• Published in: Diseases of the colon & rectum Vol. 40; no. 7; p. 785
• Main Authors: Bhatavdekar, J M, Patel, D D, Ghosh, N, Chikhlikar, P R, Trivedi, T I, Suthar, T P, Doctor, S S, Shah, N G, Balar, D B
• Format: Journal Article
• Language: English
• Published: United States 01-07-1997
• Subjects: Adult; Aged; Analysis of Variance; Antibodies, Monoclonal; Biomarkers, Tumor - analysis; Biomarkers, Tumor - genetics; Carcinoma - genetics; Carcinoma - pathology; Cell Nucleus - metabolism; Cell Nucleus - ultrastructure; Colonic Neoplasms - genetics; Colonic Neoplasms - pathology; Cytoplasm - metabolism; Cytoplasm - ultrastructure; Female; Follow-Up Studies; Gene Expression Regulation, Neoplastic; Humans; Immunoenzyme Techniques; Male; Middle Aged; Multivariate Analysis; Neoplasm Recurrence, Local - genetics; Neoplasm Recurrence, Local - pathology; Neoplasm Staging; Prognosis; Proto-Oncogene Proteins c-bcl-2 - analysis; Proto-Oncogene Proteins c-bcl-2 - genetics; Proto-Oncogene Proteins c-myc - analysis; Proto-Oncogene Proteins c-myc - genetics; Rectal Neoplasms - genetics; Rectal Neoplasms - pathology; Survival Rate; Tumor Suppressor Protein p53 - analysis; Tumor Suppressor Protein p53 - genetics
• ISSN: 0012-3706
• DOI: 10.1007/BF02055433

This study was undertaken to evaluate the clinical use of Bcl-2, c-Myc, and p53 oncoproteins, either singly or in combination, as prognostic discriminants relative to recurrence and overall survival in patients with Dukes B or C colorectal carcinoma.
Analyses were made on archival pathology tissues of 48 patients with colorectal cancer. The oncoproteins were localized using commercially available monoclonal antibodies: clone 124 for Bcl-2, 9E11 for c-Myc, and DO-7 for p53. The avidin-biotin peroxidase complex method was used. Patients were followed up for a period of 2 to 36 months.
Expression of Bcl-2 and c-Myc was cytoplasmic, whereas nuclear p53 immunoreactivity was localized in the tumor cells. Sixty percent (29/48), 65 percent (31/48), and 37 percent (18/48) of the tumors showed overexpression of Bcl-2, c-Myc, and p53 oncoproteins, respectively. Fifty-four percent (18/33) and 100 percent (9/9) of moderately and poorly differentiated tumors, respectively, were positive for Bcl-2 (P < 0.01). No such correlation was noted for c-Myc and p53 oncoproteins. Univariate analysis showed that patients with Bcl-2 and c-Myc overexpression were associated with poorer overall survival than patients with Bcl-2-negative (P < 0.0124) and c-Myc-negative (P < 0.036) tumors. In addition, when patients were subgrouped according to Dukes stage, a statistically significant poorer overall survival was observed in Dukes C patients with Bcl-2-positive tumors (P < 0.017). Furthermore, multivariate analysis revealed that coexpression of three oncoproteins was predictive of a worse prognosis than for those individuals expressing none of the oncoproteins (P < 0.031) and only one positive oncoprotein (P < 0.014).
These findings suggest that oncoprotein coexpression possesses significant prognostic and potential therapeutic value; incorporation of molecular markers into future prospective randomized trials is advisable.