Coexpression of Bcl-2, c-Myc, and p53 oncoproteins as prognostic discriminants in patients with colorectal carcinoma.
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.
Bhatavdekar
J M
JM
The Gujarat Cancer Society, Asarwa, Ahmedabad, India.
Patel
D D
DD
Ghosh
N
N
Chikhlikar
P R
PR
Trivedi
T I
TI
Suthar
T P
TP
Doctor
S S
SS
Shah
N G
NG
Balar
D B
DB
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*
D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc; D016159:Tumor Suppressor Protein p53