title: Coexpression of Bcl-2, c-Myc, and p53 oncoproteins as prognostic discriminants in patients with colorectal carcinoma.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  These findings suggest that oncoprotein coexpression possesses significant prognostic and potential therapeutic value; incorporation of molecular markers into future prospective randomized trials is advisable.
authors.affiliation: The Gujarat Cancer Society, Asarwa, Ahmedabad, India.
authors.forename: J M
authors.initials: JM
authors.lastname: Bhatavdekar
authors.forename: D D
authors.initials: DD
authors.lastname: Patel
authors.forename: N
authors.initials: N
authors.lastname: Ghosh
authors.forename: P R
authors.initials: PR
authors.lastname: Chikhlikar
authors.forename: T I
authors.initials: TI
authors.lastname: Trivedi
authors.forename: T P
authors.initials: TP
authors.lastname: Suthar
authors.forename: S S
authors.initials: SS
authors.lastname: Doctor
authors.forename: N G
authors.initials: NG
authors.lastname: Shah
authors.forename: D B
authors.initials: DB
authors.lastname: Balar
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D002277:Carcinoma / Q000235:genetics / Q000473:pathology*; D002467:Cell Nucleus / Q000378:metabolism / Q000648:ultrastructure; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology*; D003593:Cytoplasm / Q000378:metabolism / Q000648:ultrastructure; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc / Q000032:analysis / Q000235:genetics*; D012004:Rectal Neoplasms / Q000235:genetics / Q000473:pathology*; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000235:genetics*
chemical_list: D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc; D016159:Tumor Suppressor Protein p53