Prognostic value of p27, p53, and vascular endothelial growth factor in Dukes A and B colon cancer patients undergoing potentially curative surgery.
OBJECTIVE
Early-stage colon cancer patients (Dukes A or B; pT1-T3 pNO pMO) are excluded from adjuvant chemotherapy following potentially curative surgery because they are expected to have good long-term survival. However, 20 percent to 30 percent of these patients ultimately succumb from recurrent disease. This indicates that the conventional staging procedures may be unable to precisely predict cancer prognosis.


METHODS
In 65 early-stage colon cancers, we investigated by immunohistochemistry the role of molecular markers such as p27, p53, and vascular endothelial growth factor in identifying high-risk patients who may benefit from adjuvant treatments.


RESULTS
No clinicopathologic factor, namely Dukes stage, t parameter, number of resected nodes, and vascular or lymphatic invasion, was found be an independent significant predictor of disease-specific and disease-free survival. In contrast, each molecular marker predicted survival and recurrence rates much better than the conventional Dukes staging system. The best combination of variables for prediction of long-term outcome and recurrence rate included p27, p53, and vascular endothelial growth factor. Interestingly, the greater the number of molecular alterations, the lower the five-year estimated survival function. Nearly all cancer-related deaths were observed among patients whose colon cancers expressed all three molecular alterations. Regardless of Dukes stage, the recurrence rate was found to increase with the increase in the number of molecular alterations. Early-stage colon cancers expressing p27 down-regulation and high p53 and vascular endothelial growth factor immunoreactivity showed a 100 percent actuarial four-year recurrence rate.


CONCLUSIONS
Assessment of molecular alterations may be useful to identify a higher-risk group of early-stage colon cancer patients who may benefit from adjuvant chemotherapy.
Galizia
Gennaro
G
Division of Surgical Oncology, "F. Magrassi-A. Lanzara " Department of Clinical and Experimental Medicine and Surgery, Second University of Naples School of Medicine, Naples, Italy. gennaro.galizia@unina2.it
Ferraraccio
Francesca
F
Lieto
Eva
E
Orditura
Michele
M
Castellano
Paolo
P
Imperatore
Vincenzo
V
Romano
Ciro
C
Vollaro
Mario
M
Agostini
Bruno
B
Pignatelli
Carlo
C
De Vita
Ferdinando
F
D000368:Aged; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery*; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009389:Neovascularization, Pathologic; D011379:Prognosis; D016016:Proportional Hazards Models; D012044:Regression Analysis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D042461:Vascular Endothelial Growth Factor A; D050760:Cyclin-Dependent Kinase Inhibitor p27